Extra-corporeal dual stage blood processing method and apparatus

ABSTRACT

Methods and apparatus particularly involving the separation of blood into blood components and the collection of such components are disclosed. In one aspect, an extra-corporeal method for the collection of plasma and red blood cells is provided, wherein the collection of plasma and red blood cells may occur simultaneously or subsequently utilizing the same dual stage blood processing vessel. The flow of blood to the blood processing vessel and return of uncollected blood components may be provided via a single needle, wherein blood is removed from and returned to a donor/patient during alternating blood removal and blood return submodes. Platelet separation and collection options are also described. In either case, prior to red blood cell collection, a set-up phase may be carried out to set a predetermined hematocrit and AC ratio. Replacement fluid delivery may optionally also be provided either substantially continuously during any collection phase(s) and/or in a bolus mode.

CROSS REFERENCE TO RELATED APPLICATIONS

This case is a divisional of U.S. patent application Ser. No.09/803,304, filed Mar. 9, 2001, now U.S. Pat. No. 6,730,055 incorporatedherein by reference, which claims the benefit of U.S. Provisional PatentApplication No. 60/188133 filed Mar. 9, 2000.

BACKGROUND OF INVENTION

One type of extra-corporeal blood processing is an apheresis procedurein which blood is removed from a donor or patient (hereafter,donor/patient), directed to a blood component separation device (e.g.,centrifuge), and separated into various blood component types (e.g, redblood cells, white blood cells, platelets, plasma) for collection and/ortherapeutic purposes. One or more of these blood component types arecollected (e.g, for therapeutic transfusion purposes), while theremainder are preferably returned to the donor or donor/patient.

A number of factors may affect the commercial viability of an apheresissystem. One factor relates to the operator of the system, specificallythe time and/or expertise required of an individual to prepare andoperate the apheresis system. For instance, reducing the time requiredby the operator to load and unload the disposables, as well as thecomplexity of these actions, can increase productivity and/or reduce thepotential for operator error. Moreover, reducing the dependency of thesystem on the operator may lead to reductions in operator errors and/orto reductions in the credentials desired/required for the operators ofthese systems.

Donor-related factors may also impact the commercial viability of anapheresis system and include donor convenience and donor comfort. Forinstance, donors typically have a limited amount of time which may becommitted to visiting a blood component collection facility for adonation. Consequently, once at the collection facility the amount ofthe donor's time which is actually spent collecting blood components isanother factor which should be considered. This also relates to donorcomfort in that many view the actual collection procedure as beingsomewhat discomforting in that at least one and sometimes two accessneedles are disposed in the donor throughout the procedure.

Performance-related factors continue to affect the commercial viabilityof an apheresis system. Performance may be judged in terms of the“collection efficiency” of the apheresis system, which may in turnreduce the amount of donation time and thus increase donor convenience.The “collection efficiency” of a system may of course be gauged in avariety of ways, such as by the amount of a particular blood componenttype which is collected in relation to the quantity of this bloodcomponent type which passes through the apheresis system. Performancemay also be evaluated based upon the effect which the apheresisprocedure has on the various blood component types. For instance, it isdesirable to minimize the adverse effects on the blood component typesas a result of the apheresis procedure (e.g., reduce plateletactivation).

SUMMARY OF INVENTION

The present invention generally relates to extra-corporeal bloodprocessing. Since each of the various aspects of the present inventionmay be incorporated into an apheresis system (e.g, whether for bloodcomponent collection in which “healthy” cells and/or plasma are removedfrom the blood or for therapeutic purposes in which “unhealthy” cellsand/or plasma are removed from the blood), the present invention will bedescribed in relation to this particular application. However, at leastcertain of the aspects of the present invention may be suited for otherextra-corporeal blood processing applications and such are also withinthe scope of the present invention.

A typical apheresis system which may embody one or more aspects of thepresent invention would generally include a blood component separationdevice; for example, a membrane-based separation device and/or, arotatable centrifuge element, such as a rotor, which provides the forcesrequired to separate blood into its various blood component types (e.g.,red blood cells, white blood cells, platelets, and/or plasma). In onepreferred embodiment, the separation device includes a channel whichreceives a blood processing vessel. Typically, a healthy human donor ora donor/patient suffering from some type of illness (collectivelyreferred to here as a donor/patient) is fluidly interconnected with theblood processing vessel by an extra-corporeal tubing circuit, andpreferably the blood processing vessel and extra-corporeal tubingcircuit collectively define a closed, sterile system. When the fluidinterconnection is established, blood may be extracted from thedonor/patient and directed to the blood component separation device suchthat at least one type of blood component may be separated and removedfrom the blood, either for collection or for therapy.

When the blood processing vessel is loaded into the channel, the bloodprocessing vessel and most of the tubing lines must be primed. In thisregard, an aspect of the present invention relates to priming theseelements, preferably with blood. A channel associated with a channelhousing, which is rotatably interconnected with a centrifuge rotor,preferably includes a first cell separation stage. The channel extendsgenerally curvilinearly about a rotational axis of the channel housingin a first direction. The channel preferably includes, progressing inthe first direction, the first cell separation stage, a red blood celldam, a platelet and/or a plasma collection area, and an interfacecontrol region for controlling a radial position of at least oneinterface between red blood cells (RBCs) and an adjacent blood componenttype(s) (e.g., plasma and/or a buffy coat of white blood cells (WBCs),lymphocytes, and platelets). Blood introduced into the channel isseparated into layers of red blood cells (and/or a buffy coat generallyincluding white blood cells and platelets), and plasma in the first cellseparation stage. Preferably, throughout an RBC/plasma apheresisprocedure (e.g., a non-platelet procedure) and including the priming ofthe blood processing vessel, only separated plasma flows beyond the redblood cell dam where the plasma may be removed from the channel in theplasma collection area. This is provided by an interface controlmechanism which is disposed in the interface control region of thechannel and which maintains the position of the interface betweenseparated red blood cells and the plasma such that this condition ismaintained. Note, the buffy coat (platelets and WBCs) is also preferablykept behind the RBC dam in the RBC/plasma collection procedures. In thisembodiment, the buffy coat is generally collected with the RBCs and maybe either later filtered out (e.g., the WBCs by leukoreductionfiltration) or left in the RBC product (the platelets).

Although the term “blood prime” may be subject to a variety ofcharacterizations, in each case described herein, blood is the firstfluid introduced into the blood processing vessel. One characterizationof the blood prime is that separated plasma is provided to the interfacecontrol region before any separated red blood cells would ever flowbeyond the red blood cell dam into the plasma collection area.Preferably, no RBCs ever flow over the RBC dam. Another characterizationis that blood and/or blood component types occupy the entirefluid-containing volume of the blood processing vessel before anyseparated red blood cells would flow beyond the red blood cell dam intothe plasma collection area.

A further aspect of the present invention relates to blood priming anapheresis system which includes a channel housing having a bloodprocessing channel associated therewith, a blood processing vesseldisposed in the channel and which has a blood inlet port and a red bloodcell (RBC) outlet port which also acts as an interface control port. TheRBC/interface control port is used to control the radial position of atleast one interface between separated red blood cells and a bloodcomponent type(s), here preferably plasma, disposed adjacent theseparated red blood cells.

Another aspect of the present invention relates to the RBC/control portwhich assists in automatically controlling (i.e., without operatoraction) the location of an interface between the separated red bloodcells and the separated plasma relative to a red blood cell dam in theprocessing vessel. The red blood cell dam restricts the flow ofseparated red blood cells to a plasma collect port. The RBC/control portextends through the blood processing vessel and removes plasma and redblood cells as required in order to reduce the potential for red bloodcells flowing “over” the red blood cell dam to the plasma collect port.The capability of “selective” removal of red blood cells from the bloodprocessing vessel through the RBC/control port is based at least in partupon its position within the channel. That is, the automatic controlprovided at least in part by the control port is predicated upon thecontrol port assuming a predetermined radial position within thechannel. In order to facilitate achieving this predetermined radialposition within the channel, the disposition of the control port isprovided independently of the thickness of the blood processing vessel.Specifically, the position of the control port is not dependent upon thethickness of the materials which form the blood processing vessel.

Another aspect of the present invention relates to a packing factorassociated with the separated blood component types in a separationstage of the blood processing vessel. The packing factor is a numberwhich reflects the degree with which the blood component types are“packed together” in the separation stage and is dependent at least uponthe rotational speed of the channel housing and the flow rate into theblood processing vessel. The packing factor may be characterized as adimensionless “density” of sorts of the respective blood component typein the respective separation stage. One embodiment of this aspect is amethod which includes the steps of rotating the channel housing,providing a flow to the blood processing vessel in the channel housing(e.g., the flow includes blood and typically anticoagulant as well),separating the blood into a plurality of blood component types, andadjusting the rotational speed of the channel housing based upon acertain change in the flow rate. Since the packing factor is dependentupon the rotational speed of the channel housing and the flow rate intothe blood processing vessel, the methodology of this aspect may be usedto maintain a substantially constant and predetermined packing factor.In this regard, preferably the packing factor is maintained betweenabout 11 and about 15, and preferably about for collection of RBCs aloneand preferably about 16 for collection of RBCs contemporaneously withplasma.

A further aspect of the present invention relates to the extracorporealcollection of both or either plasma and red blood cells utilizing thesame blood processing vessel. More particularly, such a method includesflowing blood from a donor/patient to a blood processing vessel andseparating plasma from the blood within the blood processing vessel. Atleast a portion of the plasma is collected in a collection reservoirthat is separate from the blood processing vessel. Further, such amethod may include separating red blood cells from the blood within theblood processing vessel and collecting at least a portion of theseparated red blood cells within a red blood cell collection reservoirthat is also separate from blood processing vessel. In one approach, thecollection of plasma and red blood cells may be advantageously completedcontemporaneously, although they may also be collected during separatetime periods. For example, plasma collection may be completed prior tored blood cell collection. Alternatively, red blood cell collection mayprecede plasma collection. Note, in a continuous apheresis process, thesteps of separating and collecting may be performed substantiallysimultaneously.

In conjunction with this aspect of the present invention, and prior tothe step of collecting red blood cells, the method may further include aset-up phase during which a desired packing factor is established withinthe separated red blood cells in the blood processing vessel and adesired AC ratio may be established. Preferably, such a packing factoris established to be between about 11 and 21, and most preferably atabout 13 for collection of RBCs alone and 16 for collection of RBCscontemporaneously with plasma. Further, it is preferable that the ACratio be established to be between about 6 and 16, and most preferablyat about 8. The method may further include removing blood from adonor/patient and returning uncollected components of the blood to thedonor/patient via use of a single needle. Such removing and returningsteps may be alternately and repeatedly carried out during bloodprocessing, including during the set-up and collection phases for redblood cell collection. If the collection of plasma alone is desired, themethod may further include separating plasma from the blood within theblood processing vessel and collecting at least a portion of theseparated plasma in a separate plasma collection reservoir. Mostpreferably, plasma separation/collection may be completedcontemporaneous with the separation/collection of RBCs. Alternatively oradditionally, plasma separation/collection may be completed before orafter the separation/collection of RBCs. The use of a replacement fluidis also contemplated during collection and/or may be used in asubstantially continuous (including cycled for single needle draw/returnalternating applications) or in a bolus form.

Moreover, another aspect of the present invention involves thepresentation of versatility in providing virtually any option for thecollection of red blood cell, plasma and/or platelet products. Morespecifically, the present system can be operated such at that upon inputof the donor characteristics (e.g., height, weight, hematocrit andplatelet pre-count) the present system will return a list optionaldonations this particular donor can provide. For example, with asufficient total blood volume (calculated by the body height and weight,e.g.) and hematocrit and platelet pre-count, a donor can producepossibly several alternate and/or a plurality of products; and, thesystem can determine not only how many and what combinations of productsthis donor can donate, but also what might be preferred or prioritizedby the blood center. A sufficiently large donor may produce one or morered blood cell products and one or more plasma products and/or one ormore platelet products. Many variations of product combinations may nowbe realized. Different tubing and bag set options are also preferablypresented for such alternative collection procedures.

These and other features of the present invention will be made manifestby the detailed description and the attached drawings which are intendedto be read in conjunction with each other as set forth below.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is an isometric view of one embodiment of an apheresis systemaccording to the present invention;

FIGS. 2A-2B illustrate an alternative extracorporeal tubing circuit andcassette assembly thereof for use in the system of FIG. 1;

FIGS. 2C-2D illustrate another alternative extracorporeal tubing circuitand cassette assembly thereof for use in the system of FIG. 1;

FIG. 3 is a front view of a pump/valve/sensor assembly for the system ofFIG. 1;

FIGS. 4A-4B are cross-sectional side views of first and second pressuresensing modules of the extracorporeal tubing circuit of FIGS. 2A-2Dcoupled with corresponding pressure sensors of the pump/valve/sensorassembly of FIGS. 1 and 3;

FIG. 5 is a cross-sectional side view of the upper and lower ultrasoundsensors of the pump/valve/sensor assembly of FIG. 3 coupled with areservoir of the cassette assembly of the extracorporeal tubing circuitof FIGS. 2A-2D;

FIG. 6 is a cross-sectional side view of a platelet divert orreplacement fluid introduction valve subassembly of thepump/valve/sensor assembly of FIG. 3;

FIG. 7 illustrates a loading assembly for a cassette mounting plate ofthe pump/valve/sensor assembly of FIG. 3;

FIG. 8A is an exploded, isometric view of the channel assembly from thesystem of FIG. 1 together with a vessel such as that shown in FIGS.2A-2B;

FIG. 8B is an exploded, isometric view of a channel assembly as from thesystem of FIG. 1 together with the vessel of FIGS. 2C-2D;

FIGS. 9A-9B are top views of the channel housing from the channelassembly of FIG.

FIG. 10 is a cross-sectional view taken along line 10—10 of FIG. 9A;

FIG. 11A is a cutaway, isometric view of the platelet collect wellregion of the channel housing of FIG. 8A;

FIG. 11B is a lateral cutaway view, looking upwardly of the plateletcollect well region of the channel housing of FIG. 8A;

FIG. 12 is a cross-sectional view of the channel housing taken alongline 12—12 in FIG.

FIG. 13 is a cross-sectional view of the channel housing taken alongline 13—13 in FIG.

FIG. 14A is a top view of the blood inlet port slot, the RBC outletslot, and the control port slot on the channel housing of FIG. 8A;

FIG. 14B is a cutaway, isometric view of the whole blood inlet port slotregion of the channel housing of FIG. 8A;

FIG. 14C is a cutaway, isometric view of the control port slot region ofthe channel housing of FIG. 8A;

FIG. 15 is a top view of the channel of FIG. 8A illustrating a ratio ofthe plasma volume to the red blood cell volume;

FIG. 16 is an isometric view of the blood processing vessel of thechannel assembly of FIG. 8A in a disassembled state;

FIG. 17 is a cross-sectional view of the blood processing vessel at theinterconnection;

FIG. 18 is cross-sectional view of the blood processing vessel takenalong lines 18—18 in FIG. 16;

FIG. 19A is a cutaway, isometric view of the blood inlet port assemblyfor the blood processing vessel of FIG. 8A;

FIG. 19B is a longitudinal cross-sectional view of the blood inlet portassembly for the blood processing vessel of FIG. 8A;

FIG. 19C is a cross-sectional view of the blood inlet port assemblyinterfacing with the blood processing vessel of FIG. 8A;

FIG. 19D is an isometric view of the interior of the vane of the bloodinlet port of FIG.

FIG. 19E is a cutaway, isometric view of blood being introduced into theblood processing vessel of FIG. 8A during an apheresis procedure;

FIG. 19F is a cross-sectional view of blood being introduced into theblood processing vessel and channel of FIG. 8A during an apheresisprocedure;

FIG. 19G is a cross-sectional view, looking downwardly, of blood beingintroduced into the blood processing vessel and channel of FIG. 8Aduring an apheresis procedure;

FIG. 20A is a cutaway, isometric view of the red blood cell outlet portassembly interfacing with the blood processing vessel of FIG. 8A;

FIG. 20B is a longitudinal, cross-sectional view of the red blood celloutlet port assembly of FIG. 20A;

FIG. 20C is a cutaway, isometric view of the red blood cell portassembly interfacing with the blood processing vessel of FIG. 8A duringrinseback at the end of an apheresis procedure;

FIG. 20D is a cross-sectional view, looking downwardly, of the red bloodcell outlet port assembly interfacing with the blood processing vesselin the channel of FIG. 8A during rinseback at the end of an apheresisprocedure;

FIG. 21A is a cross-sectional view of the platelet outlet port assemblyfor the blood processing vessel of FIG. 8A;

FIG. 21B is a plan view of the platelet outlet port assembly of FIG. 21Afrom the interior of the channel;

FIG. 22 is a cutaway, isometric view of the plasma port assembly for theblood processing vessel of FIG. 8A;

FIG. 23A is a cutaway, isometric view of the control port assembly forthe blood processing vessel of FIG. 8A;

FIG. 23B is a cross-sectional view of the control port assemblyinterfacing with the blood processing vessel of FIG. 8A;

FIG. 24 is an isometric view of a centrifuge rotor assembly for thesystem of FIG. 1;

FIG. 25A is a longitudinal cross-sectional view of the rotor assembly ofFIG. 24;

FIG. 25B is a top view of the rotor body of the rotor assembly of FIG.24;

FIG. 25C is a top view of the rotor body of the rotor assembly of FIG.24 with the upper counterweight removed so as to illustrate the lowercounterweight;

FIG. 25D is a front view of the rotor body of FIG. 24;

FIG. 25E is an isometric view of the left side of the blood processingvessel aperture in the rotor body of FIG. 24;

FIG. 25F is a cross-sectional view of the rotor body of FIG. 24;

FIG. 26 is a “master screen” for the computer graphics interface of theapheresis system of FIG. 1;

FIG. 27 is a “loading procedures screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 28 is one embodiment of a “help screen” for the loading proceduresscreen of FIG.

FIG. 29 is a “disposable pressure test screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 30 is a “pressure test in progress screen” for the computergraphics interface of the apheresis system of FIG. 1;

FIG. 31 is a “AC interconnect screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 32 is the “master screen” of FIG. 26 which has been updated toreflect completion of the loading of the disposables;

FIG. 33 is a “donor/patient data screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 34 is a “weight input screen” for the computer graphics interfaceof the apheresis system of FIG. 1;

FIG. 35 is a “lab data screen” for the computer graphics interface ofthe apheresis system of FIG. 1;

FIG. 36 is the “master screen” of FIG. 26 which as been updated toreflect completion of the donor/patient preps;

FIG. 37 is a first “donor/patient preps screen” for the computergraphics interface of the apheresis system of FIG. 1;

FIG. 38 is a second “donor/patient preps screen” for the computergraphics interface of the apheresis system of FIG. 1;

FIG. 39 is a “run screen” for the computer graphics interface of theapheresis system of FIG. 1;

FIG. 40 is one embodiment of an “alarm screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 41 is a “supplemental alarm screen” for the alarm screen of FIG.40;

FIG. 42 is one embodiment of a “trouble shooting screen” for thecomputer graphics interface of the apheresis system of FIG. 1;

FIG. 43 is a “final run data display screen” for the computer graphicsinterface of the apheresis system of FIG. 1;

FIG. 44 is a “rinseback screen” for the computer graphics interface ofthe apheresis system of FIG. 1; and

FIG. 45 is an “unload screen” for the computer graphics interface of theapheresis system of FIG. 1.

DETAILED DESCRIPTION

The present invention will be described in relation to the accompanyingdrawings which assist in illustrating the pertinent features hereof.Generally, all preferred aspects of the present invention relate toimprovements in a blood apheresis system, both procedural andstructural. However, certain of these improvements may be applicable toother extracorporeal blood processing applications and such are withinthe scope of the present invention as well.

A preferred blood apheresis system 2 is illustrated in FIG. 1 andpreferably provides for a continuous blood component separation process.Generally, whole blood is withdrawn from a donor/patient 4 and isprovided to a blood component separation device 6 where the blood isseparated into the various component types and at least one of theseseparated blood component types is collected by and/or removed from thedevice 6. These collected blood components may then be provided forsubsequent use by another such as by transfusion and/or may be removedin favor of the delivery or infusion of replacement fluid(s) fortherapeutic or non-therapeutic purposes, or may undergo a therapeutictreatment and be returned to the donor/patient 4.

In the blood apheresis system 2, blood is withdrawn from thedonor/patient 4 and directed through a disposable set 8 which includesan extracorporeal tubing circuit 10 and a blood processing vessel 352and which defines a completely closed and sterile system. The disposableset 8 is mounted on the blood component separation device 6 whichincludes a pump/valve/sensor assembly 1000 for interfacing with theextracorporeal tubing circuit 10, and a channel assembly 200 forinterfacing with the disposable blood processing vessel 352.

The channel assembly 200 includes a channel housing 204 which isrotatably interconnected with a rotatable centrifuge rotor assembly 568which provides the centrifugal forces required to separate blood intoits various blood component types by centrifugation. The bloodprocessing vessel 352 is interfitted with the channel housing Blood thusflows from the donor/patient 4, through the extracorporeal tubingcircuit 10, and into the rotating blood processing vessel 352. The bloodwithin the blood processing vessel 352 is separated into various bloodcomponent types and at least one of these blood component types (e.g.,plasma, red blood cells) may preferably be continually removed from theblood processing vessel 352. Blood components which are not beingcollected for transfusion to a distinct recipient, or for therapeuticexchange or treatment (e.g., red blood cells, white blood cells, plasma,as described hereinbelow) are also removed from the blood processingvessel 352 and returned to the donor/patient 4 via the extracorporealtubing circuit 10. A continuous process here preferably includes atleast a continuously spinning/rotating vessel 352, and may also includecontinuous inflow of blood and/or outflow of separated products.

Operation of the blood component separation device 6 is preferablycontrolled by one or more processors included therein, and mayadvantageously comprise a plurality of embedded processors. Suchprocessors may be like those used in personal computers or the like,and/or preferably accommodate interface capabilities withever-increasing computer user facilities (e.g., CD ROM, modem, audio,networking and other capabilities). Relatedly, in order to assist theoperator of the apheresis system with various aspects of its operation,the blood component separation device 6 preferably includes a graphicalinterface 660 preferably with a touch screen input/output device 664.

Disposable Set: Extracorporeal Tubing Circuit

As illustrated in the alternative embodiments shown in FIGS. 2A-2D, ablood-primable extracorporeal tubing circuit 10 preferably includes acassette assembly 110 and a number of tubing assemblies 20, 50, 60, 80,90, 100, 950 and/or 960 interconnected therewith. Generally, bloodremoval/return tubing assembly 20 provides a single needle interfacebetween a donor/patient 4 and cassette assembly 110, and bloodinlet/blood component tubing subassembly 60 provides the interfacebetween cassette assembly 110 and blood processing vessel 352. As shownin the embodiment of FIGS. 2A-2B, an anticoagulant tubing assembly 50,platelet collection tubing assembly 80, plasma collection tubingassembly 90, red blood cell collection assembly 950 and vent bag tubingsubassembly 100 may be interconnected with cassette assembly 110. Asshown alternatively in the embodiment of FIGS. 2C and 2D, a variation ofRBC assembly 950 may be included, as well as a replacement fluidassembly 960 substituted generally in place of the platelet assembly 80of the embodiment of FIGS. 2A and 2B. As will be appreciated, theextracorporeal tubing circuit 10 and blood processing vessel 352/352 aare interconnected to combinatively yield a closed disposable assembly 8for a single use. Note that differences between the two primaryalternative tubing sets disclosed herein will be addressed as they arisein the course of the following description. Similarities, on the otherhand, are numerous and are not uniformly described as such hereinbelow.

The blood removal/return tubing assembly 20 includes a needlesubassembly 30 interconnected with blood removal tubing 22, blood returntubing 24 and anticoagulant tubing 26 via a common manifold 28. Theneedle subassembly 30 includes a needle 32 having a protective needlesleeve 34 and needle cap 36, and interconnect tubing 38 between needle32 and manifold needle subassembly 30 preferably further includes a Dsleeve 40 and tubing clamp positioned about the interconnect tubing 38.Blood removal tubing 22 may be provided with a Y-connector 44interconnected with a blood sampling subassembly 46.

Pump/Valve/Sensor Assembly

As noted, cassette assembly 110 is mounted upon and operativelyinterfaces with the pump/valve/sensor assembly 1000 of blood componentseparation device 6 during use. The pump/valve/sensor assembly 1000 isangled upward at about 45 degrees (see FIG. 1) and as illustrated inFIG. 3 includes a cassette mounting plate 1010, and a number ofperistaltic pump assemblies, flow divert valve assemblies, pressuresensors and ultrasonic level sensors interconnected to face plate 6 a ofblood collection device 6 for pumping, controlling and monitoring theflow of blood/blood components or replacement fluid(s) throughextracorporeal tubing circuit 10 during use.

More particularly, anticoagulant pump assembly 1020 is provided toreceive anticoagulant tubing loop 122, blood inlet pump assembly 1030 isprovided to receive blood inlet tubing loop 132, platelet or replacementfluid inlet pump assembly 1040 is provided to receive platelet orreplacement fluid tubing loop 142, plasma pump assembly is provided toreceive plasma tubing loop 162, and blood return or replacement fluiddelivery pump assembly 1090 is provided to receive blood return orreplacement fluid delivery tubing loop 192. Each of the peristaltic pumpassemblies 1030, 1040, 1060, and 1090 includes a rotor 1022, 1032, 1042,1062 and 1092, and raceway 1024, 1034, 1044, 1064, and 1094 betweenwhich the corresponding tubing loop is positioned to control the passageand flow rate of the corresponding fluid.

Platelet divert or replacement fluid valve assembly 1100 is provided toreceive platelet collector tubing 82 and platelet return tubing orreplacement fluid loop 146, plasma divert valve assembly 1110 isprovided to receive plasma collector tubing 92 and plasma return tubingloop 166, and RBC/plasma divert valve assembly 1120 is provided toreceive RBC/plasma return tubing loop 172 and RBC/plasma collectortubing 952. As noted above, each pair of tubings for collection orreturn or replacement of separated blood components is disposed in apredetermined spaced relationship within window 118 of cassette assembly110, thereby facilitating loading relative to the corresponding divertvalue assemblies. As will be further described, platelet divert orreplacement fluid valve assembly 1100, plasma divert valve assembly 1110and RBC/plasma divert valve assembly 1120 each preferably include arotary occluding member 1400 a, 1400 b and 1400 c that is selectivelypositionable between stationary occluding walls 1104 and 1106, 1114 and1116, and 1124 and 1126, respectively, for diverting fluid flow throughone tubing of the corresponding pairs of tubings.

Pressure sensors 1200 and 1260 (See also FIGS. 4A and 4B) are providedwithin pump/valve/sensor assembly 1000 to operatively engage the firstand second pressure sensing modules 134 and 138 of cassette assembly 110through openings 1120 and 1140 of cassette mounting plate 1010.Similarly, ultrasonic level sensors 1300 and 1320 (see also FIG. 5) areprovided to operatively engage the blood return reservoir 150 cassetteassembly 110 through openings 1160 and 1180 of cassette mounting plate1010.

As shown in FIGS. 4A and 4B, the first and second pressure sensingmodules 134, 138 of cassette assembly 110 each comprise a circulardiaphragm 134 a, 138 a positioned on a raised cylindrical seat 134 b,138 b formed into the back plate 114 of cassette assembly 110 with aring-shaped, plastic diaphragm retainer 134 c, 138 c hot-welded to theraised cylindrical seats 134 b, 138 b to establish a seal therebetween.This arrangement allows the diaphragms 134 a, 138 a to be directlyresponsive to the fluid pressures within the first and second integralblood inlet passageways 130 a, 130 b, respectively, and pressure sensors1200, 1260 to directly access the diaphragms 134 a, 138 a through thering-shaped retainers 134 c, 138 c. By monitoring the diaphragms 134 a,138 a, the pressure sensors 1200, 1260 can monitor the fluid pressurewithin the first and second integral blood inlet passageways 130 a, 130b. In this regard, it should also be noted that since first integralblood inlet passageway 130 a is in direct fluid communication with bloodremoval tubing 22, and since blood removal tubing 22 and blood returntubing 24 are fluidly interconnected via the common manifold 28, thefirst pressure sensing module 134 will be responsive to and firstpressure sensor 1200 will actually sense the substantially commonpressure in both the blood removal tubing 22 and blood return tubing 24during operation.

With further regard to the first pressure sensing module 134 and firstpressure sensor 1200 FIG. 4A illustrates an alternative air couplingarrangement that allows for the sensing of positive and negativepressure changes (i.e., causing outward and inward flexure of diaphragm134 a). To achieve an air seal between the first pressure sensor 1200and first pressure sensing module 134, the sensor 1200 includes aresilient (e.g., rubber), cone-shaped engaging member 1202. The engagingmember 1202 is attached to an air channel member 1204 having anipple-end 1206 that is received by beveled cylindrical extension 134 dof retainer 134 c. Air channel member 1204 further includes an outer,annular projecting channel portion 1208 that contains an O-ring 1210 forsealed sliding engagement of the air channel member 1204 within housing1212. As illustrated, housing 1212 includes ears 1214 which interfacewith a floating positioning member 1216 secured to the face plate 6 a ofblood component separation device 6. As shown, a slight clearance isprovided in such interface so as to permit slight lateral movement ofthe engaging member 1202 and air channel member 1204 during loading ofthe cassette assembly 110. A threaded end 1218 of housing 1212 extendsthrough the face plate 6 a of blood component separation device 6 andreceives nut 1220 thereupon, while leaving a slight clearance betweenthe nut 1220 and face plate 6 a. A spring 1222 is positioned within thehousing 1212 and acts upon the annular channel portion 1208 of the airchannel member 1204 to provide a spring-loaded interface between thefirst pressure sensor 1200 and first pressure sensing module 134.Pressure sensing transducer 1224 engages air channel member 1204 tosense positive and negative pressure changes within sensing module 134and provide an output signal in response thereto during use. As will befurther described, the output signal of pressure transducer 1224 can beemployed to control the operation of blood inlet pump 1030 and bloodreturn pump 1090 during operation.

With regard to the second pressure sensing module 138 and the secondpressure sensor 1260 FIG. 4B illustrates a direct contact couplingapproach that allows for sensing of positive pressure changes (i.e.,causing outward flexure of diaphragm 138 a). Such contact couplingfacilitates loading since the precise position of the diaphragm 138 arelative to the second pressure sensor 1260 is not critical. As shown,second pressure sensor 1260 includes a projecting end portion 1262 thatis received by the ring retainer of sensing module 138 to directlycontact diaphragm 138 a. Pressure transducer 1264 is mounted relative tothe face plate 6 a of the blood component separation device 6 via a ring1266 that threadingly engages a portion of pressure transducer 1264extending through the face plate 6 a. Pressure transducer 1264 providesan output signal responsive to positive pressure changes acting upondiaphragm 138 a.

As shown in FIG. 5, when cassette assembly 110 is mounted onpump/valve/sensor assembly 1000, the ultrasonic level sensors 1300 and1320 will be positioned to monitor the fluid level in the blood returnor replacement fluid reservoir 150. More particularly, upper ultrasoniclevel sensor 1300 will be positioned in contact with the reduced topsection 156 of blood return or replacement fluid reservoir 150 and lowerultrasonic level sensor 1320 will be positioned in contact with thereduced bottom section 158 of blood return or replacement fluidreservoir 150.

Ultrasonic sensors 1300, 1320 each comprise pulse/echo transducers 1302,1322 having a contact surface (e.g., urethane) 1304, 1324 thatfacilitates divert dry coupling (i.e., without a gel or other likecoupling medium) with the blood return or replacement fluid reservoir150. By way of example, ultrasonic sensors may comprise model Z-11405transducers offered by Zevex Inc. of 5175 Greenpine Drive, Salt LakeCity, Utah. Pulse/echo transducers 1302, 1322 are disposed withinhousings 1306, 1326 for interconnection with face plate 6 a of the bloodcomponent separation device 6. Housings 1326 include a flange 1308, 1328for engaging the front of face plate 6 a, and further include a threadedend 1328 that extends through the face plate 6 a to receivecorresponding retaining nuts 1310, 1330. A slight clearance is providedfor between flanges 1308, 1328 and face plate 6 a. Springs 1312, 1332are positioned within housings 1306, 1326 to act upon the correspondingpulse/echo transducers 1302, 1332 via E-clips 1314, 1334 disposedtherebetween. Such spring loading of pulse/echo transducers 1332 yieldsa predetermined desired loading pressure for pulse/echo transducers1302, 1332 relative to reservoir 150 during operation (e.g., at leastabout 5 O-rings 1316, 1336 are provided intermediate pulse/echotransducers 1302, 1322 and housings 1306, 1326 to provide a sliding sealtherebetween. Cables 1318, 1338 are interconnected to transducers 1302,1322 to provide pulsing signals and return detected echo signals.

By gauging the presence and timing of return ultrasonic echo pulses eachof the sensors 1320 can be employed to monitor the presence or absenceof fluid within their corresponding echo regions within the blood returnreservoir 150, and permit blood component separation device 6 to providepump control signals in response thereto. More particularly, when returnblood or replacement fluid accumulates up into the echo region of upperlevel sensor 1300 during blood processing, ultrasonic pulses emitted byupper level sensor 1300 will readily pass through the return blood orreplacement fluid and reflect off of the opposing reservoir outsidesidewall/air interface to yield echo pulses having a predeterminedminimum strength that are detected by upper sensor 1300 within apredetermined time period after transmission. When such echo pulses arereceived, upper sensor 1300 provides a signal that is used by bloodcomponent separation device 6 to initiate operation of blood return orreplacement fluid delivery pump 1090 so as to remove accumulated returnblood or replacement fluid from the blood return or replacement fluidreservoir 150 and transfer the same to the donor/patient 4.

When blood return or replacement fluid delivery pump 1090 has removedreturn blood or replacement fluid from the reservoir 150 down into thelower echo region, ultrasonic pulses emitted by lower level sensor 1320will not be reflected at the opposing reservoir outside sidewall/airinterface to yield echo pulses having a predetermined minimum strengthfor detection by lower level sensor 1320 within a predetermined timeperiod after transmission. When this occurs, lower level sensor 1320will fail to provide corresponding signals to blood component separationdevice 6, and blood component separation device 6 will automaticallystop blood return/replacement fluid delivery pump 1090 to stop furtherremoval of return blood/replacement fluid from the bloodreturn/replacement fluid reservoir 150, and return blood/replacementfluid will again begin accumulating in reservoir 150. Thus, in the bloodprocessing mode, blood component separation device 6 will not initiateoperation of blood return/replacement fluid delivery pump 1090 unlessand until it receives signals from upper ultrasonic sensor(theprovisions of such signals indicating the presence of return blood orreplacement fluid in the upper echo region), and will thereafterautomatically stop operation of blood return/replacement fluid deliverypump 1090 if it fails to receive signals from ultrasonic sensor 1320(the failure to receive such signals indicating the absence of returnblood or replacement fluid in the lower echo region).

In a preferable initial blood prime mode, whole blood may be introducedto reservoir 150 from a donor/patient 4 through blood return/replacementfluid delivery tubing 24 integral passageways 190 a, 190 b, and tubingloop 192 via reverse operation of blood return/replacement fluiddelivery pump 1090. When such whole blood accumulates up into the echoregion of lower level sensor 1320, ultrasonic pulses emitted by lowerlevel sensor 1320 will pass through the blood and reflect off of theopposing reservoir outside sidewall/air interface to yield echo pulseshaving a predetermined minimum strength that are detected by lower levelsensor 1320 within a predetermined time period after transmission. Whensuch echo pulses are received in the blood prime mode, lower levelsensor 1320 provides a signal that is used by blood component separationdevice 6 to turn off blood return/replacement fluid delivery pump 1090and end the blood prime mode (at least insofar as the priming of thereturn/replacement tubing 24 and reservoir 150 is concerned). Bloodcomponent separation device 6 may then initiate the blood processingmode.

It is contemplated that ultrasonic sensors 1300, 1320 can be utilizedfor indicating and/or confirming the desired mounting relationship ofcassette member 115 on cassette mounting plate 1010 for blood processingoperations. For such purposes, if the desired mounting has beenachieved, the sensors 1300, 1320 should be coupled to reservoir 150 sothat ultrasonic pulses reflect off the interface between the insidesurface of the back sidewall of reservoir 150 (i.e., the sidewallcontacted by the sensors 1300, 1320) and contained air within reservoir150, and be received with a predetermined minimum strength within apredetermined time period after transmission. If such echo pulses arereceived with respect to both ultrasonic sensors 1300, 1320, the desiredloading relationship will be indicated and/or confirmed. Further, it isnoted that ultrasonic sensors 1320 may be employable to sense echopulses from the interfaces between fluid contained within the reservoir150 and the inside surface of the outer sidewall of reservoir 150 in theupper and lower echo regions of the reservoir during operation. If suchecho pulses are detectible within corresponding, predetermined timewindows, corresponding signals provided by ultrasonic sensors 1300, 1320can provide a further input for blood component separation device 6 tocontrol operation of blood return/replacement fluid delivery pump 1090.

It should be noted that in the illustrated arrangement, the upper andlower ultrasonic sensors 1300 and 1320 advantageously operate viacoupling with reduced cross-sectional portions 156 and 158 of reservoir150. The reduced upper and lower reservoir portions 154, 158,accommodate reliable detection of echo pulses when fluid is present inthe upper and lower echo regions, and the enlarged mid-portion 158provides satisfactory return blood/replacement fluid holdingcapabilities.

FIG. 6 shows the preferred components of each of the plateletdivert/replacement fluid valve subassembly 1100, plasma divert valvesubassembly 1110 and RBC/plasma divert valve subassembly 1120. Eachsubassembly includes a rotary occluder member 1400 having a headed shaftmember 1402 and barrel sleeve 1404 positioned thereupon and rotatablerelative thereto. The subassembly further comprises a main valve shaft1406 positioned within a valve body 1408 that is secured to face plate 6a of blood component separation device 6. An O-ring 1410 is provided ina recess on the main valve shaft 1406 to provide a sliding seal betweenmain valve shaft 1406 and extensions 1412 of main valve body 1408. Themain valve shaft 1406 is driven by a motor 1414 mounted on mount plate1416 that in turn is mounted to and set off from face plate 6 a bystandoff legs 1418.

For positioning rotary occluder member 1400 for occlusion relative toone of the co-acting walls (e.g., 1104 or 1106 of the plateletdivert/replacement fluid valve sub see FIG. 3) or for loading/removal ofthe cassette assembly 110 on the blood component separation device 6,each divert valve subassembly comprises three optical through-beamsensors 1420 (two shown) interconnected to standoff legs 1418 viasupport layer 1419, and an optical interrupter member 1422interconnected to the main valve shaft Each through-beam sensor 1420 isof a U-shape configuration with a radiation source and radiationreceiver disposed on opposing legs. The optical interrupter member 1422has an inverted cup configuration with its sidewalls interposed androtatable between the opposing legs of sensors 1420. The opticalinterrupter member 1422 includes a single window 1424 therethrough. Aswill be appreciated, the position of the rotary occluder member 1400relative to the window 1424 of the optical interrupter 1422 is known,such that when the optical window 1424 passes between the opposingradiation source/receiver for a given optical sensor 1420, the opticalsensor 1420 will provide a signal in response to the through-beam(indicating the position of the rotary occluder member 1400), and thesignal is employed to control the operation of motor 1414 to disposerotary occluder member 1400 in the desired position. To provide/routesuch signals, the support layer 1419 may advantageously comprise aprinted circuit board. Optical sensors 1420 are preferably positionedslightly “upstream” of predetermined stop regions for occlusion orcassette loading so that motor 1414 will be able to dynamically slowdown and position rotary occluder member 1400 within such regions asdesired. To insure the desired positioning for occlusion, however, stops1426 are provided on main valve shaft 1406 to co-act with cross-pin 1428interconnected to main valve shaft 1406 to insure stop positioning ofrotary occluder member 1400 relative to the desired occluding wall.

Each of the occluding walls 1104 and 1106, 1114 and 1116, and 1124 and1126, are provided with arcuate recesses (not shown) for receiving therotatable barrel sleeve of rotary occluder members 1400 a, 1400 b and1400 c. By way of example, such arcuate recesses may have an arc lengthof 20 degrees and provide a tolerance range for positioning the rotaryoccluder members 1400 a, 1400 b, 1400 c to achieve the desired tubingocclusion. As illustrated in FIG. 3, occluding wall 1106 may be providedwith a resilient pad to best accommodate the use of thin-walled PVCtubing for platelet collector tubing 82. Further, and as noted above,thin-walled PVC tubing may be employed for plasma collector tubing 92and RBC/plasma collector tubing 952, and corresponding resilient pads(not shown) may be provided on occluding walls 1114 and 1124. In thisregard, given the relatively high-spring rate of thin-walled PVC tubing,the use of resilient pads in connection therewith increases thewearability of the thin-walled PVC tubing.

In order to establish an initial predetermined set position of thecassette assembly 110 relative to the pump/valve/sensor assembly 1000,the cassette assembly 110 includes downwardly extending cornerpositioning tabs 15 and top and bottom edge lips 17 110 that engagecorresponding lower channel projections 1102 a on cassette mountingplate 1010 and upper channel projections 1102 b on a pivotablespring-loaded interlock member 1104 that extends across the top edge ofcassette mounting plate 1010. The interlock member 1104 is spring-loadedto positively engage cassette assembly 110 upon loading via a springpositioned within housing 1106, and is provided with a tab 1108 forpivotable movement during cassette loading against the spring loadingpressure. Preferably, interlock member 1104 is disposed relative to theraceway 1094 of return/replacement fluid delivery pump assembly 1090,such that when cassette assembly 110 is fully loaded for operation onblood component separation device 6, raceway 1094 will physicallyrestrict interlock member 1104 from being pivoted, therebyadvantageously restricting removal and/or movement of cassette assembly110 during use.

After cassette assembly 110 has been secured on the cassette mountingplate 1010, a loading assembly 1500 retracts the cassette mounting plate1010 towards face plate 6 a of the blood component separation device 6to establish the above-noted, fully-loaded pump, valve and sensorrelationships. As illustrated in FIG. 7, loading assembly 1500 includestwo posts 1502 upon which cassette mounting plate 1010 is supportablyinterconnected. The posts 1502 extend through the face plate 6 a ofblood collection device 6 and are interconnected to a cross-connectmember 1504. A drive nut 1506 is secured to cross-connect member 1504and engages a drive screw 1508. The drive screw 1508 is in turnrotatably interconnected to a drive motor 1510 via coupling 1512, thedrive 1510 being mounted on a platform 1514 which is supportivelyinterconnected to face plate 6 a via standoff legs 1516. The drive motor1510 operates to turn drive screw 1508 so as to cause cross-connectmember 1504 and posts 1502 to selectively move cassette mounting plate1010 perpendicularly towards face plate 6 a during loading proceduresand perpendicularly away from face plate 6 a for unloading of thecassette assembly 110.

To establish the desired position of cassette mounting plate 1010,U-shaped optical through-beam sensors 1520 a and 1520 b are mounted onpost bearing holders 1522 and an optical occluder member 1524 having awindow 1526 is interconnected to the cross-connect member 1504. Each ofthe U-shaped optical sensors 1520 a, 1520 bincludes a radiation sourceand radiation receiver positioned on opposing extending legs, and theoptical occluder member 1524 extends between such legs. Since therelative positions between cassette mounting plate 1010 and opticalsensors 1520 a, 1520 b are known, by detecting the passage of radiationthrough window 1526 using optical sensors 1520, and providing a signalresponsive thereto, the position of cassette mounting plate 1010 forloading and unloading can be automatically established. For example,when a through-beam is received by optical sensor 1520 b, a signal willbe provided to stop motor 1510 in a position wherein cassette assembly110 will be fully loaded on the pump/valve/sensor assembly 1000 foroperation.

To confirm such loaded condition, first and second pressure sensors 1200and 1260 and upper and lower ultrasonic sensors 1300 and 1320 may beemployed. For example, predetermined minimum pressure values can beestablished and actual pressures measured for each of the first andsecond pressure sensors 1200 and 1260 to confirm the desired loading ofcassette assembly 110. Further, and of particular interest, ultrasonicsensors 1300 and 1320 can be advantageously employed to confirm thedesired loading, since upon proper coupling to reservoir 150 echo pulsesshould be reflected off of the internal sidewall/air interface with apredetermined minimum strength within a predetermined time period asnoted above.

It should be noted that drive motor 1510 preferably includes a number ofreduction gears with the last gear being operatively associated with aslip clutch plate to limit the maximum amount of force that may beapplied by cassette mounting plate 1010 (e.g., to an object betweencassette mounting plate 1010 and face plate 6 a). Relatedly, it ispreferable to include control capabilities wherein during a load cycleif the window 1526 of optical occluder 1524 has not moved from itsposition within the first optical pass through sensor 1520 a to aposition within the second optical pass through sensor 1520 b within apredetermined time period, drive motor 1510 will automatically eitherstop or reverse operations.

To summarize the loading process, loading assembly 1500 initiallydisposes cassette mounting plate 1010 in an extended position. With thecassette mounting plate 1010 in such extended position, interlock member1104 is pivoted away from cassette mounting plate 1010 and cassetteassembly 110 is positioned on cassette mounting plate 1010 with bottomedge lips 17 of cassette assembly 110 being received by lower channelprojections 1102 a of cassette mounting plate 1010 and, upon returnpivotal movement of interlock member 1104, top edge lips 17 of cassetteassembly 110 being engaged by upper channel projections 1102 b oninterlock member 1104. Loading assembly 1500 is then operated to retractcassette mounting plate 1010 from its extended position to a retractedposition, wherein tubing loops 132, 162, 142, 192 of cassette assembly110 are automatically positioned within the corresponding peristalticpump assemblies 1020, 1030, 1060, 1040 and 1090. For such purposes, therotors of each of the peristaltic pump assemblies are also operated toachieve loaded positioning of the corresponding tubing loops. Further,it should be noted that for loading purposes, the rotary occludermembers 1400 a, 1400 b and 1400 c of the divert valve assemblies 1100,1110 and 1120 are each positioned in an intermediate position so as topermit the corresponding sets of tubing to be positioned on each sidethereof.

Upon retraction of the cassette mounting plate 1010, spring-loaded,ultrasonic sensors 1300 and 1320 will automatically be coupled toreservoir 150 and first and second pressure sensors 1200 and 1260 willautomatically couple to first and second pressure sensing modules 134and 138 of cassette assembly 110. In this fully-loaded, retractedposition, the cassette assembly 110 will be restricted from movement orremoval by the above-noted physical restriction to pivotal movement ofinterlock member 1104 provided by raceway 1094 of return pump assembly1090.

It is also noted that during loading of cassette assembly 110 on theblood component separation device 6, cuvette 65 (whether disposed incassette 110 or in line tubing line 66 or 68) is positioned within anRBC spillover detector 1600 (e.g., an optical sensor for detecting thepresence of any red blood cells in the separated platelet or plasmafluid stream and providing a signal response thereto) provided on theface plate 6 a. Detector 1600 may also be used for set identification asdescribed hereinabove. Similarly, a portion of anticoagulant tubing 54is positioned within an AC sensor 1700 , e.g., an ultrasonic sensor forconfirming the presence of anticoagulant and providing a signal in theabsence thereof) also provided in face plate 6 a.

To unload cassette assembly 110 after use, the occluding members 1400 a,1400 b and 1400 c f each divert value assembly are again positioned inan intermediate position between the corresponding occluding walls andloading assembly 1500 is operated to move cassette mounting plate 1010from its retracted position to its extended position. Contemporaneously,the rotors of the various peristaltic pump assemblies are operated topermit the corresponding tubing loops to exit the same. In the extendedposition, the interlock member 1104 is pivoted out of engagement withcassette assembly 110 and cassette assembly 110 is removed and disposedof.

Operation of Extracorporeal Tubing Circuit and Pump/Valve/SensorAssembly

In an initial blood prime mode of operation, blood return/replacementfluid delivery pump 1090 is operated in reverse as mentioned above, totransfer whole blood from the donor/patient 4 through bloodremoval/return tubing assembly 20, integral blood return passageway 190,blood return/replacement fluid delivery tubing loop 192 and intoreservoir 150. Contemporaneously with and/or prior to the reverseoperation of blood return/replacement fluid delivery pump 1090,anticoagulant peristaltic pump 1020 is operated to prime and otherwiseprovide anticoagulant from anticoagulant tubing assembly 50, throughanticoagulant integral passageway 120, and into blood removal tubing 22and blood return tubing 24 via manifold 28. When lower level ultrasonicsensors 1320 senses the presence of the whole blood in reservoir 150 asignal is provided and blood component separation devices 6 tops bloodreturn/replacement fluid delivery peristaltic pump 1090. As will befurther discussed, during the blood prime mode blood inlet pump 1030 isalso operated to transfer blood into blood inlet integral passagewaythrough blood inlet tubing loop 132 and into blood inlet/blood componenttubing assembly 60 to prime the blood processing vessel 352.

During the blood prime mode, vent bag assembly 100 receives air fromreservoir 150. Relatedly, the occluding members 1400 a, 1400 b, 1400 cof divert assemblies 1100, 1110, 1120 are each preferably positioned todivert flow to the reservoir 150. It should also be noted that tofacilitate blood priming, the cassette assembly 110 is angled upward atabout 45 degrees in its loaded position, and the integral passageways ofcassette member 115 are disposed so that all blood and blood componentand replacement fluid inlet paths provide for a bottom-to-top bloodflow.

In the blood processing mode, the blood inlet peristaltic pump 1030,platelet/replacement fluid inlet peristaltic pump 1040 and plasmaperistaltic pump 1060 are operated generally continuously (except asdescribed hereinbelow in further detail, e.g., when operating withreplacement fluids, at least the blood inlet pump 1030 is stopped duringdelivery of replacement fluids to the donor/patient 4), and theoccluding members 1400 a, 1400 b, 1400 c are positioned for collectionor return of corresponding blood components, as desired. During a bloodremoval submode, blood return/replacement fluid delivery peristalticpump 1090 is not operated so that whole blood will pass into bloodremoval/return tubing assembly 20 and transferred to processing vessel352 via the cassette assembly 110 and blood inlet/blood component tubingassembly 60. In the blood removal submode, uncollected blood componentsare transferred from the processing vessel 352 to cassette assembly 110,and uncollected components are passed into and accumulate in reservoir150 up to a predetermined level at which upper level ultrasonic sensor1300 provides signals used by blood component separation device 6 to endthe blood removal submode and initiate a blood return or replacementfluid delivery submode. More particularly, a blood return or replacementfluid delivery submode is initiated by forward operation of bloodreturn/replacement fluid delivery peristaltic pump 1090. In this regard,it should be appreciated that in the blood return or replacement fluiddelivery submode the volume transfer rate of return blood or replacementfluid through blood return/replacement fluid tubing loop 192 utilizingblood return/replacement fluid delivery peristaltic pump 1090 isestablished by blood component separation device 6, according to apredetermined protocol, to be greater than the volume transfer ratethrough blood inlet tubing loop 132 utilizing blood inlet peristalticpump 1030 (again, in certain red blood cell collection protocols and/or,if using replacement fluid delivery, the blood inlet pump 1030 isstopped when return/delivery pump 1090 is operating). As such, theaccumulated blood or replacement fluid in reservoir 150 is transferredinto the blood return/replacement fluid delivery tubing of bloodremoval/return tubing assembly 20 and back into the donor/patient 4.During the blood processing mode, when the accumulated return blood orreplacement fluid in reservoir 150 is removed down to a predeterminedlevel, lower level ultrasonic sensor 1320 will fail to provide signalsto blood component separation device 6, whereupon blood componentseparation device 6 will automatically stop blood return/replacementdelivery peristaltic pump 1090 to end the blood return/replacementdelivery submode. This automatically serves to reinitiate the bloodremoval submode since blood inlet peristaltic pump 1030 continuouslyoperates (or restarts as described herein in replacement delivery use).

During the blood processing mode, pressure sensor 1200 sensesnegative/positive pressure changes within the blood removal tubing 22blood return/replacement delivery tubing 26, via first integral bloodinlet passageway 130 a. Such monitored pressure changes are communicatedto blood component separation device 6 which in turn controls bloodinlet pump 1030 and return pump 1090 so as to maintain fluid pressureswithin predetermined ranges during the blood removal and the bloodreturn submodes. Specifically during the blood removal submode, if anegative pressure is sensed that exceeds (i.e., is less than) apredetermined negative limit value, then blood component separationdevice 6 will slow down operation of blood inlet pump 1030 until thesensed negative pressure is back within an acceptable range. During theblood return/replacement delivery submode, if a positive pressure issensed that exceeds (i.e., is greater than) a predetermined positivelimit value, then blood component separation device 6 will preferablyslow down operation of blood return/replacement delivery pump 1090 untilthe sensed positive pressure is back within an acceptable range.

Pressure sensor 1260 monitors the positive pressure within the secondintegral blood inlet passageway 130 b and blood inlet tubing 62. If suchsensed positive pressure exceeds a predetermined maximum value, bloodcomponent separation device 6 will initiate appropriate responsiveaction, including, for example, slowing or stoppage of the centrifugeand peristaltic pumps.

During the blood processing mode, blood component separation device 6controls the operation of anticoagulant pump 1020 according to apredetermined protocol and responsive to signals provided by AC sensor1700 (e.g., indicating a depleted anticoagulant source). Also, bloodcomponent separation device 6 also controls the operation of divertassemblies 1110, 1120 according to predetermined instructions andfurther pursuant to any detect signals provided by RBC spilloverdetector 1600. In the latter regard, if an RBC spillover in theseparated platelet or plasma stream is detected, blood componentseparation device 6 will automatically cause occluder member 1400 a todivert the separated platelet or plasma stream to the return reservoir150 until the RBC spillover has cleared, thereby keeping red blood cellsfrom undesirably passing into the corresponding platelet or plasmacollector tubing assembly 80 or 90. Similarly, if a spillover detectoris used with the replacement fluid line and anything other than areplacement fluid is detected (in the embodiment of FIGS. 2 c-2 d) thenthe device 6 will take appropriate action, such as halting the procedure(even before it starts, e.g.) and prompting for a change in tubing setor fluid connection,

In normal operation, whole blood will pass through needle assembly 30,blood removal tubing 22, cassette assembly 110 and blood inlet tubing 62to processing vessel 352. As will be further described in detail, thewhole blood will then be separated into blood components in vessel 352.In the embodiment of FIGS. 2A-2B, a platelet stream will pass out ofport 420 of the vessel, through platelet tubing 66, back throughcassette assembly 110, and will then be either collected in plateletcollector assembly 80 or diverted to reservoir 150. Similarly, separatedplasma will exit vessel 352 through port to plasma tubing 68 backthrough cassette assembly 110, and will then either be collected inplasma tubing assembly 90 or diverted to reservoir 150. Further, redblood cells (and potentially white blood cells) may pass through ports492 and 520 of vessel 352 through RBC/plasma tubing 64, through cassetteassembly 110 and into reservoir 150. Alternatively, during RBCcollection procedures as described below, separated RBCs will bedelivered to RBC/plasma collector tubing assembly 950 for collection.Also, alternatively, according to the embodiment of FIGS. 2C-2D, duringproduct collection, replacement fluid will be passed through inlettubing line 962, cassette 110 and into the reservoir 150, and only RBCsand plasma will be passed out of vessel 352 through corresponding ports520 and 456 for collection and/or return as described in more detailbelow.

As noted above, when uncollected platelets, plasma, and RBC/plasma (andpotentially white blood cells) and/or replacement fluid(s) haveaccumulated in reservoir 150 up to upper ultrasonic level sensor 1300,operation of return/delivery peristaltic pump 1090 will be initiated toremove the noted blood or replacement components from reservoir 150 andtransfer the same back to the donor/patient 4 via the return/deliverytubing 24 and needle assembly 20. When the fluid level in the reservoir150 drops down to the level of the lower ultrasonic level sensor 1320,the return/delivery peristaltic pump 1090 will automatically turn offreinitiating the blood removal submode (including restarting the bloodinlet pump 1030, if necessary). The cycle between blood removal andblood return/replacement delivery submodes will then continue until apredetermined amount of platelets, RBCs or other collected bloodcomponents have been harvested.

In one embodiment, reservoir 150 and upper and lower ultrasonic sensors1300 and 1320 are provided so that, during the blood processing mode,approximately 50 milliliters of return blood/replacement fluid will beremoved from reservoir 150 during each blood return/replacement deliverysubmode and accumulated during each blood removal submode. Relatedly, insuch embodiment, lower and upper level triggering by ultrasonic sensors1300 and 1320 occurs at fluid volumes of about 15 milliliters and 65milliliters, respectively, within reservoir 150. For such embodiment, itis also believed desirable to provide for a volume transfer operatingrate range of about 30 to 300 milliliters/minute through bloodreturn/replacement delivery tubing loop 192 utilizing return/deliverypump 1090, and a volume transfer operating rate range of either zero orabout 20 to 140 milliliters/minute through blood inlet tubing loop 132utilizing blood inlet pump 1030. Additionally, for such embodiment anegative pressure limit of about −250 mmHg and positive pressure limitof about 350 mmHg is believed appropriate for controlling the speed ofinlet pump 1030 and return/delivery pump 1090, respectively, in responseto the pressures sensed in first pressure sensing module 134. A positivepressure limit of about 1350 mmHg within second sensing module 138 isbelieved appropriate for triggering slow-down or stoppage of thecentrifuge and pumps.

Channel Housing

The channel assembly 200 is illustrated in FIGS. 8A-23B and includes achannel housing 204 which is disposed on the rotatable centrifuge rotorassembly 568 (FIGS. 1 and 24) and which receives a disposable bloodprocessing vessel 352 or 352 a. Referring more specifically to FIGS.8-15, the channel housing 204 has a generally cylindrically-shapedperimeter 206 with a diameter of preferably no more than about 10 inchesto achieve a desired size for the blood component separation device 6(e.g., to enhance its portability). An opening 328 extendslongitudinally through the channel housing 204 and contains an axis 324about which the channel housing 204 rotates. The channel housing 204 maybe formed from materials such as delrin, polycarbonate, or cast aluminumand may include various cut-outs or additions to achieve weightreductions and/or rotational balance.

The primary function of the channel housing 204 is to provide a mountingfor the blood processing vessel 352 or 352 a such that the blood may beseparated into the blood component types in a desired manner. In thisregard, the channel housing 204 includes a generally concave channel 208in which the blood processing vessel 352 or 352 a is positioned. Thechannel 208 is principally defined by an inner channel wall 212, anouter channel wall 216 which is radially spaced from the inner channelwall 212, and a channel base 220 which is positioned therebetween. Thechannel 208 also extends from a first end 284 generally curvilinearlyabout a rotational axis 324 of the channel housing 204 to a second end288 which overlaps with the first end 284 such that a continuous flowpath is provided about the rotational axis 324. That is, the angulardisposition between the first end of 284 the channel 208 and the secondend 288 of the channel 208 is greater than 360 degrees and up to about390 degrees, and in the illustrated embodiment is about 380 degrees.Referring to FIG. 15, this angular disposition is measured by the angleB (beta), along a constant radius arc, between a first reference ray 336which extends from the rotational axisto 324 the first end 284, and asecond reference ray 340 which extends from the rotational axis 324 tothe second end 288 of the channel 208.

The blood processing channel vessel 352 or 352 a is disposed within thechannel 208. Generally, the channel 208 desirably allows blood to beprovided to the blood processing vessel 352/352 a during rotation of thechannel housing 204, to be separated into its various blood componenttypes by centrifugation, and to have various blood component typesremoved from the blood processing vessel 352/352 a during rotation ofthe channel housing F 204. or instance, the channel 208 is configured toallow for the use of high packing factors (e.g., generally a valuereflective of how “tightly packed” the red blood cells and other bloodcomponent types are during centrifugation and as will be discussed inmore detail below). Moreover, the channel 208 also desirably interactswith the blood processing vessel 352/352 a ring centrifugation (e.g., byretaining the blood processing vessel 352/352 a in the channel 208 andby maintaining a desired contour of the blood processing vessel I352/352 a. n addition, the channel 208 allows for a blood priming of theblood processing vessel 352/352 a (i.e., using blood as the first liquidwhich is provided to the blood processing vessel 352/352 a in anapheresis procedure).

The above-identified attributes of the channel 208 are providedprimarily by its configuration. In this regard, the channel housing 204includes a blood inlet slot 224 which is generally concave and whichintersects the channel 208 at its inner channel wall 212 insubstantially perpendicular fashion (e.g., the blood inlet slot 224interfaces with the inner channel wall 212). A blood inlet port assembly388 to the interior of the blood processing vessel 352/352 a is disposedin this blood inlet slot 224 such that blood from the donor/patient 4may be provided to the blood processing vessel 352/352 a when in thechannel 208. In order to retain a substantially continuous surface alongthe inner channel wall 212 during an apheresis procedure and with theblood processing vessel 352/352 a being pressurized, namely by reducingthe potential for the blood inlet port assembly 388 deflecting radiallyinwardly within the blood inlet slot 224, a recess 228 is disposed onthe inner channel wall 212 and contains the end of the blood inlet slot224 (e.g., FIG. 14A). This recess 228 receives a shield 408 which isdisposed about the blood inlet port assembly 388 on the exterior surfaceof the blood processing vessel 352/352 a as will be discussed in moredetail below.

As illustrated in FIGS. 8-9, an RBC dam 232 of the channel 208 isdisposed in a clockwise direction from the blood inlet slot 224 andwhose function is to preclude RBCs and other large cells such as WBCsfrom flowing in a clockwise direction beyond the RBC dam 232. Generally,the surface of the RBC dam 232 which interfaces with the fluidcontaining volume of the blood processing vessel 352/352 a may bedefined as a substantially planar surface or as an edge adjacent thecollect well 236. At least in that portion of the channel 208 betweenthe blood inlet port 224 and the RBC dam 232, blood is separated into aplurality of layers of blood component types including, from theradially outermost layer to the radially innermost layer, red bloodcells (“RBCs”), white blood cells (“WBCs”), platelets, and plasma. Themajority of the separated RBCs are removed from the channel 208 throughan RBC outlet port assembly 516 which is disposed in an RBC outlet slot272 associated with the channel 208, although at least some RBCs may beremoved from the channel 208 through a control port assembly 488 whichis disposed in a control port slot 264 associated with the channel 208.

The RBC outlet port slot 272 is disposed in a counterclockwise directionfrom the blood inlet slot 224, is generally concave, and intersects thechannel 208 at its inner channel wall 212 in substantially perpendicularfashion (e.g., the RBC outlet slot 272 interfaces with the inner channelwall 212). An RBC outlet port assembly 516 to the interior of the bloodprocessing vessel 352/352 a is disposed in this RBC outlet slot 272 suchthat separated RBCs from the apheresis procedure may be continuallyremoved from the blood processing vessel 352/352 a when in the channel208 (e.g., during rotation of the channel housing 204). In order toretain a substantially continuous surface along the inner channel wall212 during an apheresis procedure and with the blood processing vessel352/352 a being pressurized, namely by reducing the potential for theRBC outlet port assembly 516 deflecting radially inwardly within the RBCoutlet slot 272, a recess 276 is disposed on the inner channel wall 212and contains the end of the RBC outlet slot 272 (e.g., FIGS. 14A, 14B).This recess 276 receives a shield 538 which is disposed about the RBCoutlet port assembly 516 on the exterior surface of the blood processingvessel 352/352 a as will be discussed in more detail below. These aboveelements are preferably substantially similar in both of the alternativeembodiments as shown in FIGS. 8A and 8B.

In the embodiment of FIG. 8A, there is a control port slot 264 isdisposed in a counterclockwise direction from the RBC outlet slot 272,is generally concave, and intersects the channel 208 at its innerchannel wall 212 in substantially perpendicular fashion (e.g., thecontrol port slot 264 interfaces with the inner channel wall 212). Acontrol port assembly 488 to the interior of the blood processing vessel352 (see FIG. 8A) is disposed in the control port slot 264 (e.g., FIGS.14A and C). In order to retain a substantially continuous surface alongthe inner channel wall 212 during an apheresis procedure and with theblood processing vessel 352 being pressurized, namely by reducing thepotential for the control port assembly 488 deflecting radially inwardlywithin the control port slot 264, a recess 268 is disposed on the innerchannel wall 212 and contains the end of the control port slot 264. Thisrecess 268 receives a shield 508 which is disposed about the controlport assembly 488 on the exterior surface of the blood processing vessel352 as will be discussed in more detail below.

In the embodiment of FIG. 8B, the RBC outlet port 520 acts also as theinterface control outlet port, and there is thus no correspondingcontrol port assembly 488 in this embodiment. The interface controlfeatures hereof will be described further below.

The portion of the channel 208 extending between the control port slot264 and the RBC dam 232 may be characterized as the first stage 312 ofthe channel 208. The first stage 312 is configured to remove primarilyRBCs from the channel 208 by utilizing a reverse flow in relation to theflow of platelet-rich and/or platelet-poor plasma (depending upon thecorresponding use of respective vessels 352 or 352 a) through thechannel 208 which is in a clockwise direction. In this regard, the outerchannel wall 216 extends along a curvilinear path from the RBC dam 232to the blood inlet slot 224 generally progressing outwardly away fromthe rotational axis 324 of the channel housing 204. That is, the radialdisposition of the outer channel wall 216 at the RBC dam 232 is lessthan the radial disposition of the outer channel wall 216 at the bloodinlet slot 224. The portion of the RBC outlet slot 272 interfacing withthe channel 208 is also disposed more radially outwardly an the portionof the blood inlet slot 224 which interfaces with the channel 208.

In the first stage 312, blood is separated into a plurality of layers ofblood component types including, from the radially outermost layer tothe radially innermost layer, red blood cells (“RBCs”), white bloodcells (“WBCs”), platelets, and plasma. As such, the RBCs sedimentagainst the outer channel wall 216 in the first stage 312. Byconfiguring the RBC dam 232 such that it is a section of the channel 210which extends further inwardly toward the rotational axis 324 of thechannel housing 204, this allows the RBC dam 232 to retain separatedRBCs and other large cells as noted within the first stage 312. That is,the RBC dam 232 functions to preclude RBCs from flowing in a clockwisedirection beyond the RBC dam 232. And, in the embodiment of FIGS. 2C-2Dand 8B, it is preferable that, as described below, all blood componentsexcept platelet-poor plasma are precluded from flowing in a clockwisedirection beyond the RBC dam 232.

Separated RBCs and other large cells as noted are removed from the firststage 312 utilizing the above-noted configuration of the outer channelwall 216 which induces the RBCs and other large cells as noted to flowin a counterclockwise direction, e.g., generally opposite to the flow ofinlet blood into and through the first stage 312). Specifically,separated RBCs and other large cells as noted flow through the firststage 312 counter clockwise along the outer channel wall 216, past theblood inlet slot 224 and the corresponding blood inlet port assembly 388on the blood processing vessel 352/352 a, and to an RBC outlet slot 272.In the embodiment of FIG. 8A, in order to reduce the potential forcounterclockwise flows other than separated RBCs being provided to thecontrol port assembly 488 disposed in the control port slot 264 (e.g.,such that there is a sharp demarcation or interface between RBCs andplasma proximate the control port slot 264 as will be discussed in moredetail below), a control port dam 280 of the channel 208 is disposedbetween the blood inlet slot 224 and the RBC outlet slot 272. That is,preferably no WBCs, nor any portion of a buffy coat, disposed radiallyadjacent to the separated RBCs, is allowed to flow beyond the controlport dam 280 and to the control port slot 264. The “buffy coat” includesprimarily WBCs, lymphocytes, and the radially outwardmost portion of theplatelet layer. As such, substantially only the separated RBCs andplasma are removed from the channel 208 in the FIG. 8A embodiment viathe RBC control slot 264 to maintain interface control as noted.Contrarily, in the embodiment of FIGS. 2C-2D and 8B, all of these layers(except the platelet poor plasma) are retained behind the dam 232 andare also flowed back counter clockwise to the RBC/control outlet 520where all such components, even the platelet poor plasma flowing theretoin a clockwise direction from the second stage (see below), is removedthrough the RBC/control outlet 520. Preferably, as will be describedbelow, the RBC/plasma interface is maintained at the radial level of theRBC/control outlet 520; and thus, the dam 280 does not foreclose anyseparated component flow thereto.

The flow of RBCs to the control port assembly 488 in the embodiment ofFIGS. 2A-2B and 8A, is typically relatively small. Nonetheless, theability for this flow is highly desired in that the control portassembly 488 functions in combination with the RBC outlet port assembly516 to automatically control the radial position of an interface betweenseparated RBCs and the “buffy coat” in relation to the RBC dam 232 bycontrolling the radial position of an interface between separated RBCsand plasma in relation to the control port assembly 488. The controlport assembly 488 and RBC outlet port assembly 516 automaticallyfunction to maintain the location of the interface between the separatedRBCs and the buffy coat at a desired radial location within the channel208 which is typically adjacent the RBC dam 232 such that there is nospillover of RBCs or the buffy coat beyond the RBC dam 232. Thisfunction is provided by removing separated RBCs from the channel 208 ata rate which reduces the potential for RBCs and the other large cells asnoted flowing beyond the RBC dam 232 and contaminating the plateletcollection.

Separated platelets, again in the embodiment of FIGS. 2A-2B and 8A,which are disposed radially inwardly of the RBC layer and morespecifically radially inwardly of the buffy coat, flow beyond the RBCdam 232 with the plasma (e.g., via platelet-rich plasma) in a clockwisedirection. In the FIG. 8B embodiment, there is no platelet collectionperformed, and, preferably only platelet-poor plasma flows over the dam232. Forcing the interface further radially outwardly by making the RBCport 520 also act as the control port achieves this restriction, i.e.,the platelets do not get close enough to the dam 232 to flow thereoverin this other embodiment. However, in the embodiment of FIG. 8A, agenerally funnel-shaped platelet collect well 236 is disposed in aclockwise direction from the RBC dam 232 and is used to remove plateletsfrom the channel 208 in the platelet-rich plasma. The configuration ofthe platelet collect well 236 is defined by only part of the outerchannel wall 216. The portion of the platelet collect well 236 definedby the configuration of the outer channel wall 216 includes a lower face240, a left side face 244, and a right side face 248. These faces 240,244, 248 are each substantially planar surfaces and taper generallyoutwardly relative to the rotational axis 324 and inwardly toward acentral region of the platelet collect well 236.

The remainder of the platelet collect well 236 (FIG. 8A) is defined bythe blood processing vessel 352 when loaded in the channel 208, namely agenerally triangularly-shaped, which is disposed above the plateletoutlet port assembly 416 to the interior of the blood processing vessel352 and discussed in more detail below. A platelet support recessextends further radially outwardly from those portions of the plateletcollect well 236 defined by the configuration of the outer channel wall216 and primarily receives the support 428 associated with the plateletcollect port assembly 416. Generally, the upper portion of the support428 is disposed below and engages an upper lip 252 of the plateletsupport recess 249, while portions of the fourth face 444 of the support428 are seated against the two displaced shoulders 252. This positionsthe support 428 when the blood processing vessel 352 is pressurized todirect platelets toward the platelet collect port assembly 416.

The outer channel wall 216 is further configured to receive the plateletcollect tube An upper platelet collect tube recess 254 and a lowerplatelet collect tube recess 255 are disposed yet further radiallyoutwardly from the platelet support recess 249 to provide this function.As such, the platelet collect tube 424 may extend radially outwardlyfrom the outer sidewall 376 of the blood processing vessel 352, extendupwardly through the lower platelet collect tube recess 255 and theupper platelet collect tube recess 254 behind or radially outwardly fromthe support 428, and extend above the channel housing 204.

Platelet-poor plasma continues to flow in a clockwise direction throughthe channel 208 after the platelet collect well 236 (FIG. 8A), or afterthe dam 232 (in the embodiment of FIG. 8B), and may be removed from thechannel 208. In this regard, the channel 208 further includes agenerally concave plasma outlet slot 256 (FIGS. 8A and 8B) which isdisposed proximate the second end 288 of the channel 208 and intersectsthe channel 208 at its inner channel wall 212 in substantiallyperpendicular fashion (i.e., the plasma outlet slot 256 interfaces withthe inner channel wall 212). A plasma outlet port assembly 452 to theinterior of the blood processing vessel 352 is disposed in this plasmaoutlet slot 256 such that plasma may be continually removed from theblood processing vessel 352/352 a during an apheresis procedure (e.g.,during continued rotation of the channel housing 204). This plasma maybe collected and/or returned to the donor/patient 4 as described infurther detail below.

In order to increase the number of platelets that are separated andremoved from the vessel 352 in the embodiment of FIG. 8A, in a givenapheresis procedure, the configuration of the channel 208 between theplatelet collect well 236 and the plasma outlet slot 256 may be suchthat platelets which separate from plasma in this portion of the channel208 actually flow in a counterclockwise direction back towards theplatelet collect well 236 for removal from the channel 208. This may beprovided by configuring the outer channel wall 216 such that it extendsgenerally curvilinearly about the rotational axis 324 from the plateletcollect well 236 to the plasma outlet slot 256 progressing generallyinwardly toward the rotational axis 324 of the channel housing 204.Consequently, the portion of the channel 208 including the plateletcollect well 236 and extending from the platelet collect well 236 to thesecond end 288 may be referred to as a second stage 316 of the channel208. In the embodiment of FIGS. 2C-2D and 8B where there is no plateletcollect well, the second stage 316 extends from the top of the dam 232to the plasma outlet port 456 (see FIG. 2C).

The channel 208 is also configured to provide platelet-poor plasma tothe control port slot 264 in the FIG. 8A embodiment, and to theRBC/control port slot 272 in the FIG. 8 b embodiment. Thus platelet-poorplasma flows to the control port assembly 488 (FIG. 8A) or RBC/controlport 520 (FIG. 8B) in order to assist in automatically controlling theinterface between the RBCs and the buffy coat or plasma in relation tothe RBC dam I 232. n this regard, the first end 284 of the channel 208is interconnected with the second end 288 of the channel 208 by aconnector slot 260. With the first connector 360 and second connector368 of the blood processing vessel 352/352 a being joined, they may becollectively disposed in this connector slot 260. As such, a continuousflowpath is provided within the blood processing vessel 352/352 a and,for purposes of the automatic interface control feature, RBCs may flowto the control port slot 264 (FIG. 8A) in a counterclockwise directionand plasma may flow to the control port slot 264 (FIG. 8A) orRBC/control port slot 272 (FIG. 8B) in a clockwise direction. Theportion of the channel 208 extending from the first end 284 to therespective control port slots 264/272 may be referred to as a thirdstage 320 of the channel A 208.

As noted above, the configuration of the channel 208 isdesirable/important in a number of respects. As such, the dimensions ofone embodiment of the channel 208 are provided herein and which maycontribute to the functions of the channel 208 discussed below. Thedimensions for one embodiment of the channel 208 are identified on FIG.9B. All radii and thicknesses, etc., are expressed in inches.

One of the desired attributes of the channel 208 is that it facilitatesthe loading of the blood processing vessel 352/352 a therein. This isprovided by configuring the channel 208 to include a chamfer 210 on bothsides of the channel 208 along the entire extent thereof. Generally, thechamfer 210 extends downwardly and inwardly toward a central portion ofthe channel 208 as illustrated, for instance, in FIGS. 12-13. In thisembodiment the angle of this chamfer 210 ranges from about 30 degrees toabout 60 degrees relative to horizontal, and preferably is about 45degrees. Moreover, the configuration of the channel 208 retains theblood processing vessel 352/352 a within the channel 208 throughout theapheresis procedure. This is particularly relevant in that the channelhousing 254 is preferably rotated a relatively high rotationalvelocities, such as about 3,000 RPM.

Another desirable attribute of the channel 208 is that it provides aself-retaining function for the blood processing vessel 352/352 a. Theconfiguration of the channel 208 in at least the first stage 312, andpreferably in the region of the platelet collect well 236 (FIG. 8A) andin the region of the RBC dam 232 as well, is configured such that theupper portion of the channel 208 includes a restriction (e.g., such thatthe upper part of the channel 208 in this region has a reduced width inrelation to a lower portion thereof). Although this configuration couldalso be utilized in the portion of the second stage 316 disposed betweenthe platelet collect well 236 or dam 232 and the plasma outlet slot 256,in the illustrated embodiment the width or sedimentation distance of thechannel 208 in this region is less than the width or sedimentationdistance of the channel 208 throughout the entire first stage 312. Thisuse of a “reduced width” can itself sufficiently retain the bloodprocessing vessel 352/352 a in the channel 208 in the “reduced-width”portion of the second stage 316 such that the inner channel wall 212 andouter channel wall 216 in this portion of the second stage 316 may begenerally planar and vertically extending surfaces.

In the illustrated embodiment and as best illustrated in FIG. 12, thenoted “restriction” in the channel 208 is provided by configuring theouter channel wall 216 with a generally C-shaped profile. In thisportion of the channel 208, the channel 208 includes an upper channelsection 292 having a first width, a mid-channel section 300 having asecond width greater than the first width, and a lower channel section304 having a width less than that of the mid-channel section 300 andwhich is typically equal to that of the upper channel section 292. Thisprofile is provided by an upper lip 296 which extends radially inwardlyfrom the outer channel wall 216 toward, but displaced from, the innerchannel wall 212, and by a lower lip 308 which extends radially inwardlyfrom the outer channel wall 216 toward, but displaced from, the innerchannel wall 212. This lower lip 308 actually defines a portion of thechannel base 220 but does extend entirely from the outer channel wall216 to the inner channel wall 212 such that it defines a notch 218.

When the blood processing vessel 352/352 a is loaded into the channel208, the fluid-containing volume of the coinciding portion of the bloodprocessing vessel 352/352 a is disposed below the upper channel section292 and is principally contained within the mid-channel section 300.That is, the upper lip 296 “hangs over” the fluid-containing volume ofthe blood processing vessel 352/352 a over at least a portion of itslength. The upper lip 296 thereby functions to retain the bloodprocessing vessel 352/352 a within the channel 208 during rotation ofthe channel housing 204. Moreover, the upper lip 296 reduces thepotential for creep by supporting the vessel 352/352 a proximate theupper seal 380. The upper channel section 292 and the lower channelsection 304 are multi-functional in that they also serve to receive andsupport an upper seal 380 and lower seal 384 of the blood processingvessel 352/352 a to a degree such that the stresses induced on theseportions of the blood processing vessel 352/352 a during an apheresisprocedure are reduced as will be discussed in more detail below. As canbe appreciated, a similarly configured upper lip and lower lip couldextend outwardly from the inner channel wall 212 toward, but displacedfrom, the outer channel wall 216, alone or in combination with the upperlip 296 and lower lip 308, and still retain this same general profilefor the channel 208 to provide the noted functions.

Another desirable attribute of the channel 208 is that it allows for theuse of blood as the liquid which primes the blood processing vessel352/352 a versus, for instance, saline solutions. Priming with bloodallows for the actual collection of blood components to beginimmediately (i.e., blood used in the prime is separated into bloodcomponent types, at least one of which may be collected). Blood primingis subject to a number of characterizations in relation to the apheresissystem 2 and is based primarily upon the configuration of the channel F208. or instance, the configuration of the channel 208 allows for bloodto be the first liquid introduced into the blood processing vessel352/352 a which is loaded in the channel 208. Moreover, theconfiguration of the channel 208 allows separated plasma to flow in aclockwise direction through the channel 208 and to reach the controlport slot 264 (FIG. 8 a and thus the control port assembly 488 of theblood processing vessel 352) before any separated RBCs or any of theother noted large cells flow in the same clockwise direction beyond theRBC dam 232 and thus into the second stage 316 (i.e., a spillovercondition). That is, blood priming may be utilized since control of theinterface between the separated RBCs and the buffy coat is establishedbefore any RBCs or WBCs spill over into the second stage 316. Bloodpriming may also be characterized as providing blood and/or bloodcomponents to the entire volume of the blood processing vessel 352/352 aprior to any RBCs or any of the other noted large cells flowing beyondthe RBC dam 232 and into the second stage 316.

In order to achieve this desired objective of priming the bloodprocessing vessel 352/352 a with blood, generally the volume of thechannel 208 which does not have RBCs to the volume of the channel 208which does have RBCs must be less than one-half of one less than theratio of the hematocrit of the RBCs leaving the channel 208 through theRBC outlet port assembly 516 to the hematocrit of the blood beingintroduced into the channel 208 through the blood inlet port assembly388. This may be mathematically expressed as followsV ₂ /V ₁<(H _(RP) /H _(IN)−1)/2, where:

-   -   V₂=the volume of the channel 208 containing only plasma or        platelet-rich plasma;    -   V₁=the volume of the channel 208 containing RBCs of the first        stage 312 and third stage 320;    -   H_(RP)=the hematocrit of the pocked RBCs leaving the channel 208        through the RBC outlet port assembly 516; and    -   H_(IN)=the hematocrit of the blood entering the channel 208        through the blood inlet port assembly 388.

This equation assumes that the hematocrit in the RBC volume and iscalculated as (HIN+HRP)/2. In the case where the HIN is equal to 0.47and HRP is equal to 0.75, this requires that the ratio of V1/V2 be lessthan 0.30 in order for a blood prime to be possible.

The noted ratio may be further characterized as the ratio of thatportion of the channel 208 which may be characterized as containingprimarily plasma (e.g., VPL) to the volume of that portion of thechannel 208 which may be characterized as containing primarily RBCs(e.g., VRBC). Referring to FIG. 15, these respective volumes may bedefined by a reference circle 332 which originates at the rotationalaxis 324 and which intersects the RBC dam 232 at the illustratedlocation which would be at the border of a spillover condition. Portionsof the channel 208 which are disposed outside of this reference circle232 are defined as that portion of the channel 208 which includesprimarily RBCs or which defines VRBC (e.g., about 77.85 cc in theillustrated embodiment), while those portions of the channel 208 whichare disposed inside of the reference circle 232 are defined as thatportion of the channel 208 which includes primarily plasma or whichdefines VPL (e.g., about 19.6 cc in the illustrated embodiment). In theillustrated embodiment, the ratio of VPL/VRBC is about 0.25 which isless than that noted above for the theoretical calculation for the bloodprime (e.g., 0.30 based upon comparison of the hematocrits). In order tofurther achieve the noted desired ratio, the width and height of thechannel 208 throughout that portion of the second stage 316 disposed ina clockwise direction from the platelet collect well 236 (FIG. 8 a orthe dam 232 (FIG. 8B), also in third stage 320, are each less than thewidth and height of the channel 208 throughout the entire first stage312.

Another important feature relating to the configuration of the channel208 is that the radially inwardmost portion of the inner channel wall212 is at the interface with the plasma outlet slot 256. That is, theentirety of the inner channel wall 212 slopes toward the plasma outletslot 256. This allows any air which is present in the blood processingvessel 352/352 a during priming to be removed from the blood processingvessel 352/352 a through the plasma outlet slot 256 and morespecifically the plasma outlet port assembly 452 in the air will be theleast dense fluid within the blood processing vessel 352/352 a thistime.

Another desirable attribute of the channel 208 is that it contributes tobeing able to utilize a high packing factor in an apheresis procedure. A“packing factor” is a dimensionless quantification of the degree ofpacking of the various blood component types in the first stage 312 andis thus reflective of the spacings between the various blood componenttypes. The packing factor may thus be viewed similarly to a theoreticaldensity of sorts (e.g., given a quantity of space, what is the maximumnumber of a particular blood component type that can be contained inthis space).e

-   -   The packing factor is more specifically defined by the following        equation:        PF=ω ² ×R×(v _(RBC) /W)×V/Q _(IN), where:    -   PF=packing factor;    -   ω=rotational velocity;    -   R=the average radius of the outer channel wall 216 in the first        cell separation stage 312;    -   V_(RBC)=the sedimentation velocity of RBCs at 1G;    -   V=the functional volume of the first cell separation stage 312;    -   W=the average sedimentation distance or width of the channel        208; and    -   Q_(IN)=the total inlet flow to the channel 208.        Consequently, the packing factor as used herein is dependent        upon not only the configuration of the channel 208, particularly        the first stage 312, but the rotational velocities being used in        the apheresis procedure as well as the inlet flow to the blood        processing vessel 352/352 a. The following are packing factors        associated with the blood processing channel 208 having the        above-described dimensions:

N Q_(in) V G @ (rpm) ml/ml (ml) PF R_(avg) P @ R1st (psi) FF8 0 0 62.80.0 0.0 0.0 SLOPE = .02 905 5 62.8 13.0 100.1 8.1 1279 10 62.8 13.0200.2 16.2 1567 15 62.8 13.0 300.2 24.3 1809 20 62.8 13.0 400.3 32.52023 25 62.8 13.0 500.4 40.6 2216 30 62.8 13.0 600.5 48.7 2394 35 62.813.0 700.6 56.8 2559 40 62.8 13.0 800.6 64.9 2714 45 62.8 13.0 900.773.0 2861 50 62.8 13.0 1100.9 81.1 3001 55 62.8 13.0 1100.9 89.3 3001 6062.8 11.9 1100.9 89.3 3001 65 62.8 11.0 1100.9 89.3 3001 70 62.8 10.21100.9 89.3 3001 75 62.8 9.5 1100.9 89.3 3001 80 62.8 8.9 1100.9 89.33001 85 62.8 8.4 1100.9 89.3 3001 90 62.8 7.9 1100.9 89.3 3001 95 62.87.5 1100.9 89.3 3001 100 62.8 7.1 1100.9 89.3 3001 105 62.8 6.8 1100.989.3 3001 110 62.8 6.5 1100.9 89.3 3001 115 62.8 6.2 1100.9 89.3 3001120 62.8 6.0 1100.9 89.3 3001 125 62.8 5.7 1100.9 89.3 3001 130 62.8 5.51100.9 89.3 3001 135 62.8 5.3 1100.9 89.3 3001 140 62.8 5.1 1100.9 89.3

Note the G forces are listed for the various rotational speeds at themiddle of the first stage 312 and for a 10 inch outer diameter for thechannel housing 204. At about G 2,560 RPM, force is about 800 G, whileat about 3,000 RPM the G force is about 1,100 Gs.

Increasing the packing factor beyond a certain point producesdiminishing returns regarding the collection of blood component types.That is, further increases in packing factor may not producecorrespondingly increased collection efficiencies and may in fact impedethe collection of blood component types. It is believed that a packingfactor ranging from about 4 to about 21, preferably from about 11 to 16,and more preferably about 13, is optimum for collection of most bloodcomponent types. It has been observed, however, that during red bloodcell collection, an increased packing factor (i.e., >13) may provedesirable to lower the level of white blood cells in the collected RBCproduct. A packing factor of 16 has been found preferable in collectingRBCs and plasma simultaneously with the embodiment of FIGS. 2C-2D and 8B(see below). The rotational velocity of the channel housing 204 may beadjusted based upon the inlet flows being provided to the bloodprocessing vessel 352 or 352 a to maintain the desired packing factor.For instance, the desired operating speed for the centrifuge housing 204during the normal course of an apheresis procedure is preferably about3,000 RPM. However, this rotational speed may be reduced to “match” theinlet flow to the blood processing vessel 352 or in order to retain thedesired packing factor. Similarly, the rotational speed of the channelhousing 204 may be increased to “match” an increased inlet flow to theblood processing vessel 352/352 a in order to retain the desired packingfactor.

Due to constraints regarding the blood processing vessel 352/352 a, morespecifically the various tubes interconnected therewith (e.g., whichprovide the seal-less loop), the above-noted desired packing factors ofabout 13 may be realized for inlet flows of up to about 55 ml/min.(instantaneous). Beyond 55 ml/min., the rotational speed would have tobe increased above 3000 RPM to maintain the desired packing factor ofabout 13. Although tubes exist which will withstand those rotationalspeeds, presently they are not approved for use in an apheresis system.With the presently approved tubing, the packing factor may be maintainedat a minimum of about 10, and preferably at least about 10.2, or even11, for inlet flows (instantaneous) of about 40-70 ml/min. For thepacking factor preference of 16 for the collection of RBCs and plasmatogether (FIGS. 2C-2D), a maximum 3000 RPM rotational speed wouldindicate that a slower inlet flow would be necessary. The higher packingfactor of 16 provides a purer plasma separation (i.e., fewer platelets)over the RBC dam; and thus, a purer plasma product. However, a packingfactor of 16 is also slower because of the lower inlet flow. Thus, aftercollecting plasma and RBCs together (until a minimum desired amount ofplasma is collected, for instance), then the packing factor wouldpreferably be reduced to about 13 to collect RBCs at a faster rate.

The packing factor may also be related to the resulting hematocritachieved by the system. A target hematocrit of 80, for example, has beenreadily achievable with a packing factor of preferably between 11 and16, and again preferably about 13. Note, the resulting hematocrit isalso dependent on the amount of separated plasma which is re-mixed withthe separated RBCs in the interface control outlets, as describedherein.

At the above noted increased rotational speeds, the channel 208 not onlyprovides for achieving an increased packing factor, but reduces theimpact of this high packing factor on the collection efficiencyregarding platelet collection. Specifically, the configuration of thechannel 208 is selected to reduce the number of platelets that areretained within the first stage 312 (in FIG. 8A embodiment). Theconfiguration of the channel 208 in the first stage 208 utilizes aprogressively reduced width or sedimentation distance progressing fromthe blood inlet slot 224 to the RBC dam 232. That is, the width of thechannel 208 proximate the blood inlet slot 224 is less than the width ofthe channel 208 proximate the RBC dam 232. This configuration of thechannel 208 in the first stage 312 reduces the volume of the “buffycoat” or more specifically layer between the RBCs and platelets to becollected. As noted, this buffy coat includes primarily WBCs andlymphocytes, as well as the radially outwardmost portion of the plateletlayer. The “buffy coat” is preferably retained in the first stage 312during an apheresis procedure. Since the volume of the “buffy coat” isreduced by the reduced width of the channel 208 proximate the RBC dam232, this reduces the number of platelets which are retained in thefirst stage(FIG. 8A), and thus increases the number of platelets whichflow to the platelet collect well 236 (FIG. 8A).

Disposable Set: Blood Processing Vessel

The blood processing vessel 352 (or 352 a in the FIG. 2C, 8B embodiment)is disposed within the channel 208 for directly interfacing with andreceiving a flow of blood in an apheresis procedure. The use of theblood processing vessel 352/352 a alleviates the need for sterilizationof the channel housing 204 after each apheresis procedure and the vessel352/352 a may be discarded to provide a disposable system. There areinitially two important characteristics regarding the overall structureof the blood processing vessel 352/352 a. The blood processing vessel352/352 a is constructed such that it is sufficiently rigid to befree-standing in the channel 208. Moreover, the blood processing vessel352/352 a is also sufficiently rigid so as to be loaded in the channel208 having the aboveidentified configuration (i.e., such that the bloodprocessing vessel 352/352 a must be directed through the reduced widthupper channel section 292 before passage into the larger widthmid-channel section 300). However, the blood processing vessel 352/352 amust also be sufficiently flexible so as to substantially conform to theshape of the channel 208 during an apheresis procedure.

In order to achieve the above-noted characteristics, the bloodprocessing vessel 352/352 a may be constructed as follows. Initially,materials for the blood processing vessel 352/352 a include PVC, PETG,and polyolefins, with PVC being preferred. Moreover, the wall ofthickness of the blood processing vessel 352/352 a will typically rangebetween about 0.030″ and 0.040″. Furthermore, the durometer rating ofthe body of the blood processing vessel 352/352 a will generally rangefrom about 50 Shore A to about 90 Shore A.

Referring primarily to FIGS. 16-23B, the blood processing vessel 352/352a includes a first end 356 and a second end 364 which overlaps with thefirst end 356 and is radially spaced therefrom. A first connector 360 isdisposed proximate the first end 356 and a second connector 368 isdisposed proximate the second end 364. When the first connector 360 andsecond connector 368 are engaged (typically permanently), a continuousflow path is available through the blood processing vessel 352/352 a.This construction of the blood processing vessel 352/352 a facilitatesloading in the channel 208 in the proper position and as noted alsocontributes to the automatic control of the interface between theseparated RBCs and the buffy coat or plasma relative to the RBC dam 232.

The blood processing vessel 352/352 a includes an inner sidewall 372 andan outer sidewall 376. In the illustrated embodiment, the bloodprocessing vessel 352/352 a is formed by sealing two pieces of materialtogether (e.g., RF welding). More specifically, the inner sidewall 372and outer sidewall 376 are connected along the entire length of theblood processing vessel 352/352 a to define an upper seal 380 and alower seal 384. Seals are also provided on the ends of the vessel352/352 a. The upper seal 380 is disposed in the reduced width upperchannel section 292 of the channel 208, while the lower seal 384 isdisposed in the reduced width lower channel section 304 of the channel208 (e.g., FIG. This 19F). again reduces the stresses on the upper seal380 and lower seal 384 when a flow of blood is provided to the bloodprocessing vessel 352/352 a and pressurizes the same. That is, the upperseal 380 and lower seal 384 are effectively supported by the channel 208during an apheresis procedure such that a resistance is provided to a“pulling apart” of the upper seal 380 and lower seal 384. By utilizingtwo separate sheets to form the blood processing vessel 352/352 a, a“flatter” profile may also be achieved. This type of profile isbeneficial during rinseback, and also facilitates loading and unloadingof the vessel 352/352 a relative to the channel 208.

Blood is introduced into the interior of the blood processing vessel352/352 a through a blood inlet port assembly 388 which is moreparticularly illustrated in FIGS. 19 a-g.

Initially, the port 392, as all other ports, is welded to the bloodprocessing vessel 352/352 a over a relatively small area. This resultsin less movement of materials due to the welding procedure whichprovides a smoother surface for engagement by the blood and/or bloodcomponent types.

The blood inlet port assembly 388 includes a blood inlet port 392 and ablood inlet tube 412 which is fluidly interconnected therewithexteriorly of the blood processing vessel 352/352 a. The blood inletport 392 extends through and beyond the inner sidewall 372 of the bloodprocessing vessel 352/352 a into an interior portion of the bloodprocessing vessel 352/352 a. Generally, the blood inlet port assembly388 is structured to allow blood to be introduced into the bloodprocessing vessel 352/352 a during an apheresis procedure withoutsubstantially adversely affecting the operation of the apheresis system2.

The blood inlet port 392 includes a substantially cylindrical sidewall396. A generally vertically extending slot 404 is disposed proximate anend of the sidewall 396 of the blood inlet port 392 such that the slot404 is substantially parallel with the inner sidewall 372 and outersidewall 376 of the blood processing vessel 352/352 a. The slot 404projects in the clockwise direction, and thus directs the flow of bloodin the channel 208 generally toward the RBC dam 232. A vane 400 ispositioned on the end of the cylindrical sidewall 396, is disposed to besubstantially parallel with the inner sidewall 322 and thereby directsthe flow of blood out through the slot 404. As illustrated in FIG. 19D,the vane 400 includes a generally V-shaped notch on the interior of theblood inlet port 392, the arcuate extent of which defines the “height”of the slot 404.

The desired manner of flow of blood into the blood processing vessel352/352 a during an apheresis procedure is subject to a number ofcharacterizations, each of which is provided by the above-describedblood inlet port assembly 388. Initially, the flow of blood into theblood processing vessel may be characterized as being at an angle ofless than 90 degrees relative a reference line which is perpendicular tothe inner sidewall 372 of the blood processing vessel 352/352 a. Thatis, the blood is injected in a direction which is at least partially inthe direction of the desired flow of blood through the blood processingvessel 352/352 a. Moreover, the desired flow of blood into the bloodprocessing vessel 352/352 a may be characterized as that which reducesthe effect on other flow characteristics within blood processing vessel352/352 a at the blood inlet port 392.

Separated RBCs 556 again flow along the outer sidewall 376 of the bloodprocessing vessel 352/352 a adjacent the outer channel wall 216, pastthe blood inlet port 392 and the RBC outlet port assembly 516 asillustrated in FIGS. 19E and 19G. The desired flow of blood into theblood processing vessel 352/352 a may then be further characterized asthat which is substantially parallel with at least one other flow in theregion of the blood inlet port 392 (e.g., inject the blood substantiallyparallel with the flow of RBCs 556). This manner of introducing bloodinto the blood processing vessel 352/352 a may then be furthercharacterized as that which does not significantly impact at least oneother flow in the region of the blood inlet port 392.

As noted above, the blood inlet port assembly 388 interfaces with theinner sidewall 372 of the blood processing vessel 352/352 a in a mannerwhich minimizes the discontinuity along the inner channel wall 212 inthe region of the blood inlet slot 224 in which the blood inlet port 392is disposed. Specifically, a shield 408 may be integrally formed withand disposed about the blood inlet port 392. The shield 408 is disposedon an exterior surface of the blood processing vessel 352/352 a andinterfaces with its inner sidewall 372. The shield 408 is at least inpartial overlapping relation with the inner sidewall 372. Moreover, inthe case where the shield 408 is integrally formed with the port 392, itneed not be attached to the inner sidewall 372. The port 392 isinstalled asymmetrical relative to the shield 408 which is beneficialfor manufacturability. All shields and their blood-related portsdiscussed below also include this feature.

Generally, the shield 408 is more rigid than the inner sidewall 372 ofthe blood processing vessel 352/352 a. This increased rigidity may beprovided by utilizing a more rigid material for the shield 408 than isused for the inner sidewall 372. For instance, the durometer rating ofthe material forming the shield 408 may range from about 90 Shore A toabout 130 Shore A, while the durometer rating of the material formingthe inner sidewall 372 of the blood processing vessel 352/352 a againranges from about 50 Shore A to about 90 Shore A in one embodiment. Thisdurometer rating (when the shield 408 and port 392 are integrallyformed) also enhances the seal between the port 392 and the tubeinstalled therein.

When the blood inlet port 392 is disposed in the blood inlet slot 224when loading the blood processing vessel 352/352 a in the channel 208,the shield 408 is positioned within the recess 228 formed in the innerchannel wall 212. Again, the blood inlet slot 224 intersects with theinner channel wall 212, and more specifically the recess 228. That is,the recess 228 contains and is disposed about one end of the blood inletslot 224. Preferably, the thickness of the shield 408 is substantiallyequal to the depth or thickness of the recess 228 such that the amountof discontinuity along the inner channel wall 212 in the region of theblood inlet slot 224 is reduced or minimized. Due to the increasedrigidity of the shield 408 in comparison to the materials forming theblood processing vessel 352/352 a, when the blood processing vessel352/352 a is pressurized during an apheresis procedure the shield 408restricts movement of the blood processing vessel 352/352 a and/or theblood inlet port 392 into the blood inlet slot 224. That is, the shield408 restricts and preferably minimizes any deflection of the bloodprocessing vessel 352/352 a into the blood inlet slot 224 during theprocedure. Moreover, with the shield 408 being integrally formed withthe blood inlet port 392, the radial position of the vertical slot 404in the blood inlet port 392 is not dependent upon the thickness of thematerials forming the blood processing vessel 352/352 a.

In the first stage 312, blood which is provided to the blood processingvessel 352/352 a by the blood inlet port assembly 388 is separated intoat least RBCs, and plasma. The RBCs, as well as most of the WBCs, areretained within the first stage 312 and are preferably precluded fromflowing in a clockwise direction past the RBC dam 232 into the secondstage 316 or, in the FIG. 8A embodiment, into the platelet collect wellInstead, the RBCs and WBCs are induced to flow along the outer channelwall 216 in a counterclockwise direction past the blood inlet port 392and toward the RBC outlet port assembly 516 of the blood processingvessel 352/352 a. That is, the RBC outlet port assembly 516 is disposedin a counterclockwise direction from the blood inlet port assembly 388.However, as noted above, in the FIG. 8A embodiment, the control port dam280 impedes the flow to the buffy coat control port assembly 488 toprovide a sharp interface between the separated RBCs and the plasmaproximate the control port assembly 488 such that this may be used tocontrol the radial position of the interface between the RBCs and thebuffy coat in the area of the RBC dam 232. In the FIG. 8B embodiment onthe other hand, the interface is established proximate the RBC/controlport 520 as described hereinbelow.

The RBC outlet port assembly 516 is more specifically illustrated inFIGS. 20A-D and generally includes an RBC outlet port 520 and an RBCoutlet tube 540 fluidly interconnected therewith exteriorly of the bloodprocessing vessel 352/352 a. The RBC outlet port 520 extends through andbeyond the inner sidewall 372 of the blood processing vessel 352/352 ainto an interior portion of the blood processing vessel 352/352 a. Inaddition to removing separated RBCs from the blood processing vessel352/352 a during an apheresis procedure, the RBC outlet port assembly516 also functions in combination with the control port assembly 488(FIG. 8A) or by itself (FIG. 8B) to automatically control the radialposition of the interface between separated RBCs and the buffy coat orplasma relative to the RBC dam 232 (i.e., to prevent RBCs from flowingbeyond the RBC dam 232) in a manner discussed in more detail below.

The RBC outlet port 520 is also configured to reduce the potential forthe flow therethrough being obstructed during rinseback (i.e, during theevacuation of the blood processing vessel 352/352 a upon completion ofblood component separation and collection process so as to provide asmuch of the contents thereof back to the donor/patient 4). Duringrinseback, the rotation of the channel housing 204 is terminated and arelatively significant drawing action (e.g., by pumping) is utilized toattempt to remove all contents from the blood processing vessel 352/352a. The end of the RBC outlet port 520 includes a first protrusion 524and a second protrusion 528 displaced therefrom, with a central recess532 being disposed therebetween which contains the noted orifice 536 forthe blood outlet port 520. The first protrusion 524 and the secondprotrusion 528 each extend further beyond the inner sidewall 372 of theblood processing vessel 352/352 a a greater distance then the centralrecess 532/352 a. As such, during rinseback if the outer sidewall 376attempts to contact the inner sidewall 372, the first protrusion 524 andsecond protrusion 528 will displace the central recess 532 and itsorifice 536 away from the outer sidewall 376. This retains the orifice536 in an open condition such that the flow therethrough is notobstructed during rinseback.

As noted above, the RBC outlet port assembly 516 interfaces with theinner sidewall 372 of the blood processing vessel 352/352 a in a mannerwhich minimizes the discontinuity along the inner channel wall 212 inthe region of the RBC outlet 272 in which the RBC outlet port 520 isdisposed. Specifically, a shield 538 is integrally formed with anddisposed about the RBC outlet port 520. The shield 538 is disposed on anexterior surface of the blood processing vessel 352/352 a and interfaceswith its inner sidewall 372. The shield 538 is at least in partialoverlapping relation with the inner sidewall 372. Moreover, in the casewhere the shield 538 is integrally formed with the port 520, it need notbe attached to the inner sidewall 372. Generally, the shield 538 is morerigid than the inner sidewall 372. This increased rigidity may beprovided by utilizing a more rigid material for the shield 538 than isused for the inner sidewall 372. For instance, the durometer rating ofthe material forming the shield 538 may range from about 90 Shore A toabout 130 Shore A, while the durometer rating of the material formingthe inner sidewall 372 of the blood processing vessel 352/352 aagainranges from about 50 Shore A to about 90 Shore A in one preferredembodiment.

When the RBC outlet port 520 is disposed in the RBC outlet slot 272 whenloading the blood processing vessel 352/352 a in the channel 208, theshield 538 is positioned within the recess 276 formed in the innerchannel wall 212. Again, the RBC outlet slot 272 intersects with theinner channel wall 212, and more specifically the recess That is, therecess 276 contains and is disposed about one end of the RBC outlet slot272. Preferably, the thickness of the shield 538 is substantially equalto the depth or thickness of the recess 276 such that the amount ofdiscontinuity along the inner channel wall 212 in the region of the RBCoutlet slot 272 is reduced or minimized. Due to the increased rigidityof the shield 538 in comparison to the materials forming the bloodprocessing vessel 352/352 a, when the blood processing vessel 352/352 ais pressurized during an apheresis procedure, the shield 538 restrictsmovement of the blood processing vessel 352/352 a and/or the RBC outletport 520 into the RBC outlet slot 272. That is, the shield 538 restrictsand preferably minimizes any deflection of the blood processing vessel352/352 a into the RBC outlet slot 272. Moreover, with the shield 538being integrally formed with the RBC outlet port 520, the radialposition of the orificeis not dependent upon the thickness of thematerials forming the blood processing vessel 352/352 a.

Separated platelets in the embodiment of FIG. 8A, are allowed to flowbeyond the RBC dam 232 and into the second stage 316 of the channel 208in platelet-rich plasma. The blood processing vessel 352 (FIG. 8A)includes a platelet collect port assembly 416 to continually removethese platelets from the vessel 352 throughout an apheresis procedureand such is more particularly illustrated in FIGS. 8A, 16, and 21A-B.Generally, the platelet collect port assembly 416 is disposed in aclockwise direction from the blood inlet port assembly 388, as well asfrom the RBC dam 232 when the blood processing vessel 352 is loaded intothe channel 208. Moreover, the platelet collect port assembly 416interfaces with the outer sidewall 376 of the blood processing vessel352.

The platelet collect port assembly 416 (FIG. 8A) is disposed in theplatelet support recess 249 and the platelet outlet tube recess 254which are disposed radially outwardly from the portion of the plateletcollect well 236 defined by the outer channel wall 216 of the channel208. The platelet collect port assembly 416 generally includes aplatelet collect port 420 and a platelet collect tube 424 which isfluidly interconnected therewith exteriorly of the blood processingvessel 352. The orifice 422 of the port 420 may be substantially flushwith the interior surface of the outer sidewall 376 of the bloodprocessing vessel 352. Moreover, the radial position of the orifice 422is established by engagement of part of the platelet collect port 420with boundaries of the recess 249 and/or 254.

The platelet collect port 420 (FIG. 8A) is welded to the bloodprocessing vessel 352. The thickness of the overlapping portions of theport 420 and vessel 352 are substantially equal. The weld area isoverheated such that there is a mixing of the two materials. Thisresults in the platelet collect port 420 being able to flexsubstantially against the outer channel wall 216 when the vessel 352 ispressurized.

The blood processing vessel 352 (FIG. 8A) and the outer channel wall 216of the channel 210 collectively define the platelet collect well 236.The contribution of the blood processing vessel 352 to the plateletcollect well 236 is provided by a substantially rigid support 428 whichis disposed vertically above the platelet collect port 420 and hingedlyinterconnected at location 430 with the outer sidewall 376 and/or amounting plate 426 of the platelet collect port 420. The contouredsupport 428 includes a first face 432 and a second face 436 whichinterface with the exterior surface of the outer sidewall 376 of theblood processing vessel 352 (i.e., the support overlaps with thesidewall 376 of the blood processing vessel 352 and need not be attachedthereto over the entire interface therewith) and which are disposed indifferent angular positions. The upper portion of the first face 432extends over the top of the blood processing vessel 352, while the lowerportion of the first face 432 generally coincides with the upper seal380 on the blood processing vessel 352. The second face 436 interfaceswith the outer sidewall 376 in a region of the fluid-containing volumeof the blood processing vessel 352 and is the primary surface whichdirects platelets toward the platelet collect port 420.

When the blood processing vessel 352 (FIG. 8A) is pressurized, thesupport 428 moves into a predetermined position defined by portions ofthe platelet collect recess 252. Specifically, a third face 440 isretained under an upper lip 254 on the upper perimeter of the plateletsupport recess 249, and the two sides of a fourth face 444 seat againsta shoulder 252 disposed on each side of the platelet support recess 249.A platelet tubing notch 448 is formed in the support 428 at generallythe intersection between the third face 440 and the fourth face 444. Theplatelet collect tube 426 thus may extend out from the platelet collectport 420, up the platelet collect tube recess 254, against the platelettube notch 448 if necessary, and above the channel housing 204 to passdown through the central opening 328 therein.

In order to increase the purity of platelets that are collected, aplatelet purification system as described in U.S. patent applicationSer. Nos. 08/423,578 and corresponding U.S. Pat. Nos. 5,674,173;5,906,570; inter alia, and 08/423,583 may be disposed in the plateletcollect tube 424 of the embodiment of FIGS. 2A-2B and 8A, and the entiredisclosures of these patent documents are incorporated by reference intheir entirety herein.

Platelet-poor plasma flows beyond the platelet collect well 236 (FIG.8A) and/or beyond the dam 232 (FIG. 8B) and to the plasma outlet portassembly 452. Here, some of the platelet-poor plasma may be removed fromthe blood processing vessel 352/352 a and collected, although this“separated” plasma may also be returned the donor/patient 4 in someinstances. The plasma port 456 is also used in the blood priming of thevessel 352/352 a in that air is removed from the vessel 352/352 athrough the plasma port 456. Referring to FIG. 22, the plasma outletport assembly 452 includes a plasma outlet port 456 and a plasma outlettube 476 which is fluidly interconnected therewith exteriorly of theblood processing vessel 352/352 a. The plasma outlet port 456 extendsthrough and beyond the inner sidewall 372 of the blood processing vessel352/352 a into an interior of the blood processing vessel 352/352 a. Theplasma outlet port 456 is disposed between the second end 364 of theblood processing vessel 352/352 a and the second connector 368.

The plasma outlet port 456 is configured to reduce the potential for theflow therethrough being obstructed during rinseback (i.e., duringevacuation of the blood processing vessel 352/352 a upon completion ofan apheresis procedure so as to provide as much of the contents thereofback to the donor/patient 4). During rinseback, the rotation of thechannel housing 204 is terminated and a relatively significant drawingaction (e.g., by pumping) is utilized to attempt to remove all contentsfrom the blood processing vessel The end of the plasma outlet port 456includes a first protrusion 460 and a second protrusion 464 displacedtherefrom, with a central recess 468 being disposed therebetween whichcontains an orifice 472 for the plasma outlet port 456. The firstprotrusion 460 and the second protrusion 464 each extend further beyondthe inner sidewall 372 of the blood processing vessel 352/352 a agreater distance then the central recess 468. As such, during rinsebackif the outer sidewall 376 attempts to contact the inner sidewall 372,the first protrusion 460 and second protrusion 464 will displace thecentral recess 468 and its orifice 472 away from the outer sidewall 376.This retains the orifice 472 in an open condition such that the flowtherethrough is not obstructed during rinseback.

In order to further assist in withdrawal from the blood processingvessel 352/352 a after completion of an apheresis procedure and thusduring rinseback, a first passage 480 and a second passageway 484 (seeFIGS. 8A, 8B and 16) are formed in the blood processing vessel 352/352 a(e.g., via heat seals, RF seals) and generally extend downwardly fromthe plasma outlet port 456 toward a lower portion of the bloodprocessing vessel 352/352 a. The first passageway 480 and secondpassageway 484 are disposed on opposite sides of the plasma outlet port456. With this configuration, a drawing action through the plasma outletport 456 is initiated in a lower portion of the blood processing vessel352/352 a at two displaced locations.

Some of the separated plasma is also utilized to automatically controlthe location of the interface between separated RBCs and the buffy coator plasma in the first stage 312, specifically the radial position ofthis interface relative to the RBC dam 232. Plasma which provides thisinterface control function is removed from the blood processing vessel352 by a control port assembly 488 in the embodiment of FIGS. 2A-2B and8A, and which is illustrated in FIGS. 23A-B. (Again, the embodiment ofFIGS. 2C-2D and 8B does not preferably have a control port assembly488.) The control port assembly 488 is disposed in a clockwise directionfrom the plasma outlet port assembly 452 and proximate the RBC outletport assembly 516, and thus between the first end 284 of the channel 208and the RBC outlet port assembly 516. This plasma thus flows from thesecond stage 316 and into the third stage 320 to provide this function.

The control port assembly 488 (FIG. 8A) generally includes a controlport 492 and control port tube 512 which is fluidly interconnectedtherewith exteriorly of the blood processing vessel 352. The controlport 492 extends through and beyond the inner sidewall 372 of the bloodprocessing vessel 352 into an interior portion of the blood processingvessel 352. The radial positioning of the orifice 504 of the controlport 492 is not dependent upon the thickness of the material forming theblood processing vessel Instead, the control port 492 includes ashoulder 496 which engages or seats upon structure within the controlport slot 264 to accurately place the orifice 504 at a predeterminedradial position within the channel 208. Moreover, this predeterminedradial position is substantially maintained even after the bloodprocessing vessel is pressurized. In this regard, the control portassembly 488 interfaces with the inner sidewall 372 of the bloodprocessing vessel 352 in a manner which minimizes the discontinuityalong the inner channel wall 212 in the region of the control port slot264 in which the control port 492 is disposed. Specifically, a shield508 is integrally formed with and disposed about the control port 492.The shield 508 is disposed on an exterior surface of the bloodprocessing vessel 352 and interfaces with its inner sidewall 372. Theshield 508 is at least in partial over-lapping relation with the innersidewall 372. Moreover, in the case where the shield 508 is integrallyformed with the port 492, it need not be attached to the inner sidewall372. Generally, the shield 508 is more rigid than the inner sidewall 372and this assists in maintaining the orifice 504 of the control port 492at the desired radial position within the channel 208. This increasedrigidity may be provided by utilizing a more rigid material for theshield 508 than is used for the inner sidewall 372. For instance, thedurometer rating of the material forming the shield 508 may range fromabout 90 Shore A to about 130 Shore A, while the durometer rating of thematerial forming the inner sidewall 372 of the blood processing vessel352 again ranges from about 50 Shore A to about 90 Shore A in oneembodiment.

The control port assembly 488 (FIG. 8A) and/or the RBC outlet portassembly 516 (by itself in the FIG. 8B embodiment) function incombination to control the radial position of the interface betweenseparated RBCs and the buffy coat or plasma relative to the RBC dam 232.In the FIG. 8A embodiment, two structural differences between the RBCoutlet port assembly 516 and the control port assembly 488 contribute toachieving this automatic control. Initially, the orifice 536 to the RBCoutlet port 520 is disposed further into the interior of the bloodprocessing vessel 352 than the control port 492. In one embodiment, theorifice 536 of the RBC outlet port 520 is disposed more radiallyoutwardly than the orifice 504 of the control port 492. Moreover, thediameter of the RBC outlet tube 540 is greater than that of the controlport tube 512. In one embodiment, the inner diameter of the RBC outlettube 54 is about 0.094″, while the inner diameter of the control porttube 512 is about 0.035″. The control port tube 512 and RBC outlet tube540 also join into a common return tube 546 via a three-way tubing jack544 which further assists in providing the automatic interface controlfeature.

The automatic interface position control is provided as followsutilizing the RBC outlet port assembly 516 and the control port assembly488 in FIG. 8A. Initially, there are two interfaces in the channel 208of significance with regard to this automatic interface position controlfeature. One of these interfaces is the RBC/buffy coat interface inrelation to the RBC dam 232. However, there is also an RBC/plasmainterface in the region of the control port assembly 488 which again isavailable through use of the control port dam 280. The control port dam280 allows substantially only RBCs to flow to the control port assembly488 in a counterclockwise direction.

In the event that the interface between the RBCs and plasma movesradially inwardly toward the rotational axis 324, RBCs will beginflowing out the control port tube 512 in addition to the RBC outlet tube540. This decreases the flow through the smaller diameter control porttube 512 due to the higher viscosity and density of the RBCs compared tothe plasma which typically flows through the control port tube 512.Consequently, the flow through the larger diameter RBC outlet tube 540must increase since the flow through the return tube 546 must remain thesame. This removes more RBCs from the first stage 312 such that both theinterface between the RBCs and the buffy coat in relation to the RBC dam232 and the interface between the RBCs and the plasma both move radiallyoutwardly. That is, this changes the radial position of each of theseinterfaces. As such, the potential for RBCs flowing beyond the RBC dam232 and into the platelet collect well 236 is reduced.

In the event that the location of the interface between the RBCs andplasma progresses radially outward, the flow through the control porttube 512 will increase since the quantity of RBCs exiting the bloodprocessing vessel 352 through the control port 512 will have decreased.Since the flow through the return tube 546 must remain the same, thisresults in a decrease in the flow of RBCs through the RBC outlet tube540. This reduces the number of RBCs being removed from the channel 208such that both the interface between the RBCs and the buffy coat inrelation to the RBC dam 232 and the interface between the RBCs and theplasma both move radially inwardly. That is, this changes the radialposition of each of these interfaces.

The above-described tubes which interface with the blood processingvessel 352 of the embodiment of FIGS. 2A-2B and 8A, namely the bloodinlet tube 412, the platelet collect tube 424, the plasma outlet tube476, the return tube 546, each pass downwardly through the centralopening 328 in the channel housing 204. A tubing jacket 548 is disposedabout these various tubes and protects such tubes during rotation of thechannel housing 204. These tubes are also fluidly interconnected withthe extracorporeal tubing circuit 10 which again provides for fluidcommunication between the donor/patient 4 and the blood processingvessel 352.

The blood processing vessel 352/352 a also includes features for loadingand unloading the same from the channel 208. Referring back to FIG. 16,the vessel 352/352 a includes at least one and preferably a plurality oftabs 552. The tabs 552 may be integrally formed with the bloodprocessing vessel 352/352 a (e.g., formed by the seal which also formsthe upper seal 380). However, the tabs 552 may also be separatelyattached. The tabs 552 nonetheless extend vertically above thefluid-containing volume of the blood processing vessel 352/352 a,preferably a distance such that the tabs 552 actually project above thechannel housing 204. The tabs 552 thereby provide a convenientnon-fluid-containing structure for the operator to grasp and load/removethe blood processing vessel 352/352 a into/from the channel 208 (e.g.,they provide structure for the operator to grasp which has had noblood-related flow therethrough during the apheresis procedure). Thetabs 552 are particularly useful since there may be resistance providedto a loading and an unloading of the blood processing vessel 352/352 ainto/from the channel 208.

Centrifuge Rotor Assembly

The channel assembly 200 is mounted on the centrifuge rotor assembly 568which rotates the channel assembly 200 to separate the blood into thevarious blood component types by centrifugation. The centrifuge rotorassembly 568 is principally illustrated in FIGS. 24-25 and generallyincludes a lower rotor housing 584 having a lower gear 588. An input ordrive shaft 576 is disposed within the lower rotor housing 584 and isrotatably driven by an appropriate motor 572. The input/drive shaft 576includes a platform 580 mounted on an upper portion thereof and a rotorbody 592 is detachably interconnected with the platform 580 such that itwill rotate therewith as the input/drive shaft 576 is rotated by themotor 572.

The centrifuge rotor assembly 568 further includes an upper rotorhousing 632 which includes a mounting ring 644 on which the channelhousing 204 is positioned. In order to allow the channel housing 204 torotate at twice the speed of the rotor body 592, the upper rotor housing632 and lower rotor housing 584 are rotatably interconnected by a pinionassembly 612. The pinion assembly 612 is mounted on the rotor body 592and includes a pinion mounting assembly 616 and a rotatable pinion 620.The pinion 620 interfaces with the lower gear 588 and a driven gear 636which is mounted on the mounting ring 644. The gear ratio is such thatfor every one revolution of the rotor body 592 the upper rotor housing632 rotates twice. This ratio is desired such that no rotary seals arerequired for the tubes interfacing with the blood processing vessel Inone embodiment, the lower gear 588, the pinion 620, and the driven gear636 utilize straight bevel gearing.

The centrifuge rotor assembly 568 is also configured for easy loading ofthe blood processing vessel 352/352 a in the channel 208 of the channelhousing 204. In this regard, the rotor body 592 includes a generallyL-shaped blood processing vessel loading aperture 597. The aperture 597includes a lower aperture 600 which extends generally horizontally intothe rotor body 592 through its sidewall 596 of the rotor body 592, butonly partially therethrough. The perimeter of the lower aperture 600 isdefined by a left concave wall 601, a back concave wall 603, and a rightconcave wall 602.

The loading aperture 597 also includes an upper aperture 598 whichintersects with the lower aperture 600 at 599 and extends upwardlythrough an upper portion of the rotor body 592. The upper aperture 598is aligned with a generally vertically extending central opening 640 inthe upper rotor housing 632. As noted above, the channel housing 204also includes a central opening 328. As such, a blood processing vessel352/352 a may be folded if desired, inserted into the lower aperture600, deflected upwardly by the back concave wall 603, through the upperaperture 598, through the central opening 640 in the upper rotor housing632, and through the central opening 328 of the channel housing 204. Theoperator may then grasp the blood processing vessel 352/352 a and loadthe same in the channel 208.

The centrifuge rotor assembly 568 includes a number of additionalfeatures to facilitate the loading of the blood processing vessel352/352 a in the channel 208. Initially, the pinion 620 is radiallyoffset in relation to the lower aperture 600 of the rotor body 592. Inone embodiment, a reference axis laterally bisects the lower aperture600 and may be referred to as the “zero axis”. The axis about which thepinion 620 rotates is displaced from this “zero axis” by an angle α ofabout 40 degrees in the illustrated embodiment (see FIG. 25A). An angleα of −40 degrees could also be used. Positioning the pinion 620 at anangle of “greater” than ±40 degrees will result in the pinion 620beginning to interfere with the access to the loading aperture 597.Although the angle α may be less than 40 degrees and may even be 0degrees, having the pinion 620 at 0 degrees will result in thecounterweights 608 potentially interfering with the access to theloading aperture 597. Based upon the foregoing, in FIG. 25 the pinionassembly 612 has therefore been rotated about the axis which thecentrifuge rotor assembly 568 rotates for ease of illustration.

Since only a single drive gear is utilized to rotate the upper rotorhousing 632 relative to the rotor body 592, an upper counterweight 604and lower counterweight 608 are disposed or detachably connected to therotor body 592 proximate the upper and lower extremes of the loweraperture 600. Due to the offset positioning of the pinion 620 inrelation to the lower aperture 600, the upper and lower counterweights604, 608 are also radially offset in relation to the lower aperture 600.That is, the upper and lower counterweights 604, 608 are “off to theside” in relation to the lower aperture 600 such that access thereto isnot substantially affected by the counterweights 604 and 608. A tubemounting arm 624 is also appropriately attached to the rotor body 592and engages the tubing jacket 548. The tubing mounting arm 624 serves tofurther the rotational balance of the rotor body 592.

Another feature of the centrifuge rotor assembly 568 which contributesto the loading of the blood processing vessel 352/352 a upwardly throughthe rotor body 592 is the size of the lower aperture 600. As illustratedin FIG. 25B, the “width” of the lower aperture may be defined by anangle θ which may range from about 70 degrees to about 90 degrees, andin the illustrated embodiment is about 74 degrees. The back wall 603,left wall 601 and right wall 602 are also defined by a radius rangingfrom about “1.75”to about “2.250”, and in the illustrated embodimentthis radius is between about “2.008” and about “2.032”.

Apheresis Protocol

A first alternative protocol which may be followed for performing anapheresis procedure on a donor/patient 4 utilizing the above-describedsystem 2 will now be summarized. Initially, an operator loads thecassette assembly 110 onto the pump/valve/sensor assembly 1000 of theblood component separation device 6 and hangs the various bags (e.g.,bags 104, 94, 84, and/or 954) on the blood component separation device6. The operator then loads the blood processing vessel 352 (e.g., FIGS.2A, 2B and 8 a) within the channel 208 which is disposed on the channelhousing 204 which is in turn mounted on the centrifuge rotor assembly568, particularly the mounting ring 644. More specifically, the operatormay fold the blood processing vessel 352 and insert the same into theblood processing vessel loading aperture 597 on the rotor body 592. Dueto the arcuately-shaped, concave configuration of the loading aperture597, specifically the lower aperture 600, the blood processing vessel352 is deflected upwardly through the upper aperture 598, the centralopening 640 in the upper rotor housing, and the central opening 328 inthe channel housing 294. The operator then grasps the blood processingvessel 352 and pulls it upwardly away from the channel housing 204.

Once the blood processing vessel 352 has been installed up through thecentrifuge rotor assembly 568, the operator loads the blood processingvessel 352 into the channel 208 on the channel housing 204. The operatorgenerally aligns the blood processing vessel 352 relative to the channel208 (e.g., such that the blood inlet port 392 is vertically aligned withthe blood inlet slot 224, such that the platelet collect port 420 isvertically aligned with the platelet support recess 249 and the plateletcollect tube recess 254 (in the embodiment of FIGS. 2A-2B), such thatthe plasma outlet port 456 is vertically aligned with the plasma outletslot 256, such that the control port 492 is vertically aligned with thecontrol port slot 264 (also per FIGS. 2A-2B), and such that the RBCoutlet port 520 is vertically aligned with the RBC outlet slot 272).Once again, the interconnection of the first connector 360 and secondconnector 368, which is preferably fixed, facilitates the loading of theblood processing vessel 352, as well as the existence of the chamfer210.

With the blood processing vessel 352 properly aligned, the operatordirects the blood processing vessel 352 through the reduced width upperchannel section 292 of the channel 208 until the blood processing vessel352 hits the channel base 220. In this case, the longitudinal extent ofthe blood processing vessel 352 located in the portion of the channel208 which includes the first stage 312, the RBC dam 232, and theplatelet/plasma collect or second stage 316 will be disposed asfollows: 1) the upper seal 380 will be disposed in the upper channelsection 292; 2) the fluid-containing volume of the blood processingvessel 352 will be disposed in the mid channel section 300; and 3) thelower seal 384 will be disposed in the lower channel section 304. Theabove-noted ports will also be disposed in their respective slots in thechannel housing 204 by the operator at this time. Moreover, the shield408 associated with the blood inlet port assembly 388 will be disposedin the recess 228 associated with the blood inlet slot 224. Similarly,the shield 538 associated with the RBC outlet port assembly 516 will bedisposed in the recess 276 associated with the RBC outlet slot 272.Furthermore, the shield 508 associated with the control port assembly488 will be disposed in the recess 268 associated with the control portslot 264 (according to the embodiment of FIGS. 2A-2B).

With the extracorporeal tubing circuit 10 and the blood processingvessel 352 loaded in the above-described manner, the circuit 10 andvessel 352 may first be pressure-tested to verify that there are noleaks. The donor/patient 4 is then fluidly interconnected with theextracorporeal tubing circuit 10 (by inserting an access needle 32 intothe donor/patient 4). Moreover, the anticoagulant tubing 54 is primedbetween the anticoagulant supply (which interfaces with the spike dripmember 52) and the manifold 48. Furthermore, blood return/replacementdelivery tubing 28 is primed with blood from the donor/patient 4 byrunning the blood return/replacement delivery peristaltic pump 1090 pumpin reverse to draw blood from the donor/patient 4, through the bloodreturn tubing 28, and into the reservoir 150 until blood is detected bythe low level sensor 1320.

The blood processing vessel 352 must also be primed for the apheresisprocedure. In one embodiment, a blood prime may be utilized in thatblood will be the first liquid introduced into the blood processingvessel 352. The flow of blood from the donor/patient 4 to theextracorporeal tubing circuit 10 is initiated with the centrifuge rotorassembly 568 rotating the channel housing 204 at a rotational velocityof from about 150 RPM to about 250 RPM for a rotor diameter of about10″, and typically about 200 RPM. This lower rotational velocity notonly reduces the potential for air locks developing the in the bloodprocessing vessel 352, but also minimizes any preheating of the bloodprocessing vessel 352. The rotational velocity in this “first stage”need not be fixed, but may vary.

Once the flow of blood reaches the blood processing vessel 352, therotational speed of the channel housing 204 is increased from about1,500 RPM to about 2,500 RPM for a rotor diameter of about 10″,preferably about 2000 RPM, such that blood being provided to the bloodprocessing vessel 352 will be separated into the various blood componenttypes even during the priming procedure. Once again, in this “secondstage”, the rotational velocity need not be fixed, but may vary. Inorder for a blood prime to be successful in the first embodiment, a flowmust be provided to the control port assembly 488 before any RBCs flowsbeyond the RBC dam 232 in a clockwise direction. This is again providedby the configuration of the channel 208. When there is no control portassembly 488 (see FIGS. 2C-2D), a plasma flow first desirably reachesthe RBC/control port 520 before RBCs flow over or beyond the RBC dam 232(although this is less important in this embodiment as described below).

Importantly, during this “second stage” of the blood priming procedure,air present in the blood processing vessel 352 is removed from the bloodprocessing vessel 352 and due to the noted rotational velocities in this“second stage”, the potential for air locks is also reduced. Morespecifically, air which is present in the blood processing vessel 352 isless dense than the whole blood and all of its blood component types. Asnoted above, the radially inwardmost portion of the inner channel wall212 is at the intersection between the plasma outlet slot 256 and theinner channel wall 212. Consequently, the air present in the bloodprocessing vessel 352 collects near the plasma outlet port 456 and isremoved from the blood processing vessel 352 through the plasma outlettubing 476, and is provided to the vent bag 104.

When the blood processing vessel 352 contains blood and/or bloodcomponents throughout its entirety, the rotational velocity of thechannel housing 204 is increased to its normal operation speed fromabout 2,750 RPM to about 3,250 RPM for a rotor diameter of about 10″,and preferably about 3,000 RPM. This completes the blood primingprocedure.

During the above-noted blood priming procedure, as well as throughoutthe remainder of the apheresis procedure, blood component types areseparated from each other and removed from the blood processing vessel352 on a blood component type basis. At all times during the apheresisprocedure, the flow of whole blood is provided to the blood processingvessel 352 through the blood inlet port assembly 416 and is directed tothe first stage 312. The control port dam 280 again reduces thepotential for blood flowing in a counterclockwise direction in thechannel 208 in the FIG. 8A embodiment. Other detailed differences ofblood priming between the embodiments disclosed herein will be furtheraddressed below.

In the first stage 312, blood is separated into a plurality of layers ofblood component types including, from the radially outermost layer tothe radially innermost layer, RBCs, WBCs, platelets, and plasma. Assuch, the RBCs sediment against the outer channel wall 216 in the firstcell separation stage 312. By configuring the RBC dam 232 such that itis a section of the channel 210 which extends further inwardly towardthe rotational axis 324 of the channel housing 204, this allows the RBCdam 232 to retain separated red blood cells in the first stage 312.

Separated RBCs are removed from the first stage 312 utilizing theabove-noted configuration of the outer channel wall 216 which inducesthe RBCs to flow in a counterclockwise direction (e.g., generallyopposite to the flow of blood through the first cell separation stage312). That is, the portion of the channel 208 proximate the RBC outletport assembly 516 is disposed further from the rotational axis 324 ofthe channel housing 204 than that portion of the channel 210 proximatethe RBC dam 232. As such, separated RBCs flow through the first stage312 in a counterclockwise direction along the outer channel wall 216,past blood inlet port assembly 388 on the blood processing vessel 352and to an RBC outlet port assembly 516. Since the vertical slot 404 ofthe blood inlet port 392 is substantially parallel with the innerchannel wall 212, the outer channel wall 216, the inner sidewall 372 ofthe blood processing vessel 352 and the outer sidewall 376 of the bloodprocessing vessel 352, since it directs the flow of blood in a clockwisedirection in the channel 208 and thus toward the RBC dam 232, and sinceit is disposed proximate the inner channel wall 212, the introduction ofblood into the blood processing vessel 352 does not substantially affectthe flow of RBCs along the outer channel wall 216. Consequently, RBCseffectively flow undisturbed past the blood inlet port 392 and to theRBC outlet port assembly 516 for removal from the blood processingvessel 352. These RBCs may either be collected and/or provided back tothe donor/patient 4.

An embodiment such as the first embodiment described herein(corresponding to FIGS. 2A-2B and FIG. 8A) may make use of the fact thatplatelets are less dense then RBCs and are thus able to flow beyond theRBC dam 232 when the RBC/buffy coat interface is disposed sufficientlyclose to the dam 232 (i.e., sufficiently radially inwardly disposed tobe near the top of the dam 232). These platelets would then flow to theplatelet collect well 236 in platelet-rich plasma where they are removedfrom the blood processing vessel 352 by the platelet collect portassembly 416. Again, the blood processing vessel 352 via the support 428and the outer channel wall 216 would collectively define the plateletcollect well 236 when the blood processing vessel 352 is pressurized.That is, part of the platelet collect well 236 is defined by the lowerface 240 and side faces 244, 248 formed in the outer channel wall 216,while the remainder thereof is defined by the second face 436 of thesupport 428 when the support 428 is moved into a predetermined positionwithin and against portions of platelet support recess 249 uponpressurization of the blood processing vessel 352.

Platelet-poor plasma is less dense than the platelets and would continueto flow in a clockwise direction through the second stage 316 to theplasma outlet port assembly 452 where at least some of the plasma isremoved from the blood processing vessel 352. This plasma may becollected and/or returned to the donor/patient 4. However, some of theplasma flow continues in the clockwise direction into and through thethird stage 320 to the control port assembly 488 to provide forautomatic control of the location of the interface between the RBCs andplatelets in the above-described manner. As described further below,preferably all of the plasma which flows over the RBC dam 232 in thesecond embodiment herein (FIGS. 2C-2D) would be platelet-poor and flowto the plasma outlet port assembly 452 as above, as well as to theRBC/control outlet port 520 even though there is no control portassembly 488.

Platelet/RBC (and Potential Plasma) Collection

As noted, a preferred blood apheresis system 2 provides forcontemporaneous separation of a plurality of blood components duringblood processing, including the separation of red blood cells (RBCs),platelets and plasma. In turn, such separated blood components may beselectively collected in corresponding storage reservoirs (or bags) orimmediately returned to the donor/patient 4 during a blood returnsubmode. In this regard, and in one approach where at least plateletsand/or both platelets and RBCs (and/or potentially plasma) are to becollected (see the embodiment of FIGS. 2A-2B), blood apheresis system 2may be advantageously employed to collect platelets, and if desiredseparated plasma, during a time period(s) separate from the collectionof red blood cells. In this manner, the collection of both high qualityplatelet units and high quality red blood cell units can be realized.

Moreover, the procedures described herein are preferably carried outusing blood priming of extracorporeal tubing circuit 10 and bloodprocessing vessel 352. Also, the preferred blood processing hereprovides for the collection of platelets in reservoir 84 during a firstperiod and the collection of red blood cells in reservoir 954 during asecond period (FIGS. 2A-2B). Plasma collection in reservoir 94 may alsobe selectively completed during the first period. During the plateletblood processing period and successive RBC collection procedure, bloodcomponent separation device 6 will control the initiation andtermination of successive blood removal and blood return submodes, asdescribed hereinabove. Additionally, blood component separation device 6will control the platelet and RBC collection processes according to apredetermined protocol, including control over the divert valveassemblies 1100, 1110 and 1120 of the pump/valve/sensor assembly 1000.

More particularly, following blood priming, blood separation controldevice 6 provides control signals to pump/valve/sensor assembly 1000 sothat in the embodiment of FIGS. 2A-2B, platelet divert valve assembly1100 diverts the flow of separated platelets pumped through plateletoutlet tubing 66 and platelet tubing loop 142 into platelet collectiontubing 82 for collection in reservoir 84. If plasma collection isdesired, blood component separation device 6 also provides controlsignals so that plasma divert valve 1110 diverts the flow of separatedplasma pumped through plasma outlet tubing 68 and plasma tubing loop 162into plasma collector tubing 92 for collection in reservoir 94.Additionally, RBC/plasma divert valve assembly 1120 will continue todivert the flow of separated RBCs flowing through outlet tubing 64through return tubing loop 172 and into blood return reservoir 150.Platelet collection is carried out as previously discussed hereinabove,with a packing factor in the second stage of vessel 352 maintained atbetween about 4 and 15, and most preferably at about 13. When thedesired volumes of platelets and plasma have been collected, bloodcomponent separation device 6 will selectively control divert assembliesand 1110 to divert the flow of platelets and plasma into reservoir 150.

Preferably following completion of platelet and plasma collection (inthe embodiment of FIGS. 2A-2B), the RBC collection procedure isinitiated via control signals provided by blood collection device 6.Such RBC collection procedure includes a setup phase and a collectionphase. During the setup phase, the blood apheresis system 2 is adjustedto establish a predetermined hematocrit in those portions of the bloodprocessing vessel 352 and extracorporeal tubing circuit 10 through whichseparated RBCs will pass for collection during the RBC collection phase.

More particularly, during the setup phase, and in order to realize apredetermined hematocrit of at least about 75%, for example, and morepreferably at about 80%, the packing factor in the first stage 312 ofthe blood processing vessel 352 is established at between about 11 andabout 21, and most preferably at about 13. Additionally, the AC ratio(i.e., the ratio between the inlet flow rate to vessel 352 (includingwhole blood plus anticoagulant AC) and the AC flow rate into tubingcircuit 10) will be established within the range of about 6 to 16, andmost preferably at about 8.14 (particularly in the U.S.). Further, thetotal uncollected plasma flow rate through blood processing vessel 352and extracorporeal tubing circuit 10 will be established at apredetermined level. These adjustments are carried out in simultaneousfashion to establish the desired hematocrit in an expeditious manner. Aswill be appreciated, the adjusted AC ratio and predetermined hematocritshould be maintained during the subsequent RBC collection phase.

During the set-up phase, blood component separation device 6 providesappropriate control signals to the pump/valve/sensor assembly 1000 suchthat all separated blood components flowing out of processing vessel 352will pass to return reservoir 150. Also, blood component separationdevice 6 will continue operation of blood inlet pump assembly 1030,including operation during each blood return submode.

In order to establish the desired packing factor, the operating speed ofcentrifuge rotor assembly 568 may be selectively established via controlsignals from blood component separation device 6, and the blood inletflow rate to vessel 352 may be selectively controlled via control byblood component separation device 6 over pump assembly 1030. Moreparticularly, as mentioned above, increasing the rpms of centrifugerotor assembly 568 and/or decreasing the inlet flow rate will tend toincrease the packing factor, while decreasing the rpms and increasingthe flow rate will tend to decrease the packing factor. As can then beappreciated, the blood inlet flow rate to vessel 352 is effectivelylimited by the desired packing factor.

To establish the desired AC ratio, blood component separation device 6provides appropriate control signals to anticoagulant peristaltic pump1020 so as to introduce anticoagulant into the blood inlet flow at apredetermined rate, as previously described hereinabove. Relatedly, inthis regard, it should be noted that the inlet flow rate ofanticoagulated blood to blood processing vessel 352 is limited by apredetermined, maximum acceptable anticoagulant infusion rate (ACIR) tothe donor/patient 4. As will be appreciated by those skilled in the art,the predetermined ACIR may be established on a donor/patient-specificbasis (e.g., to account for the particular total blood volume of thedonor/patient 4).

To establish the desired total uncollected plasma flow rate out of bloodprocessing vessel 352, blood collection device 6 provides appropriatecontrol signals to plasma pump assembly 1060 and platelet pump assembly1040. Relative to platelet collection, such control signals willtypically serve to increase plasma flow through plasma outlet port 456,and thereby reduce plasma flow with RBCs through RBC outlet port 520.This serves to increase the hematocrit in the separated RBCs.Additionally, it is preferable for blood processing device 6 to providecontrol signals to platelet pump assembly 1040 so as to establish apredetermined flow rate wherein platelets and some plasma pass togetherthrough platelet port 420, thereby reducing platelet clumping downstreamin tubing circuit 10. In this regard, such predetermined rate will belimited by the diameter of the platelet outlet tubing 66 and the size ofthe internal channels (e.g., 140 a, 140 b) within molded cassette 110.

In one embodiment, where centrifuge rotor assembly 568 defines a rotordiameter of about 10 inches, and where a blood processing vessel 352(FIGS. 2A-2B) is utilized, as described hereinabove, it has beendetermined that channel housing 204 can be typically driven at arotational velocity of about 3000 rpms to achieve the desired hematocritduring the setup and blood collection phases. Correspondingly, the bloodinlet flow rate to vessel 352 should be established at or below about64.7 ml/min. The desired hematocrit can be reliably stabilized bypassing about two whole blood volumes of either reservoir 150 (incassette 110) or reservoir 352 through the respective reservoir beforethe RBC collection phase is initiated.

To initiate the RBC collection phase, blood component separation device6 provides an appropriate control signal to RBC/plasma divert valveassembly 1120 so as to direct the flow of RBCs removed from bloodprocessing vessel 352 into RBC collection reservoir 954. Both theplatelet divert valve assembly 1100 and plasma divert valve assembly1110 remain in a position to direct flow into reservoir 150 for returnto donor/patient 4 during blood return submodes. In the later regard, itis preferable that, during blood return submodes of the RBC collectionphase, blood collection device 6 provide appropriate control signals soas to stop the operation of all pump assemblies other than return pumpassembly 1090. In this regard, stoppage of inlet pump assembly 1030avoids recirculation of uncollected blood components into vessel 352 andresultant dilution of separated RBC components within vessel 352.

As will be appreciated, in the present invention separated RBCs are notpumped post-separation out of vessel 352 for collection, but instead arepushed out vessel 352 and through extracorporeal tubing circuit 10 bythe pressure of the blood inlet flow to vessel 352. Consequently, traumato the collected RBCs is minimized.

During the RBC collection phase, the inlet flow into vessel 352 islimited by the above-noted maximum acceptable ACIR to the donor/patient4. The desired inlet flow rate is also limited by that necessary tomaintain the desired packing factor, as also discussed. In this regard,it will be appreciated that, relative to the setup phase, the inlet flowrate may be adjusted slightly upwards during the RBC collection phasesince not all anticoagulant is being returned to the donor/patient 4.That is, a small portion of the AC remains with the plasma that iscollected with the RBCs in RBC reservoir 954.

Following collection of the desired quantity of red blood cells, bloodseparation device 6 may provide a control signal to divert assembly1120, so as to divert RBC flow to reservoir 150. Additionally, iffurther blood processing is not desired, rinseback procedures may becompleted. Additionally, the red blood cell reservoir 954 may bedisconnected from the extracorporeal tubing circuit 10. A storagesolution may then be added. Such storage solution may advantageouslyfacilitate storage of the RBCs for up to about 42 days at a temperatureof about 1-6 degrees C. In this regard, acceptable storage solutionsinclude a storage solution generically referred to in the United Statesas Additive Solution(AS-3), available from Medsep Corp. located inCovina, Calif.; and a storage solution generically referred to in Europeas “SAGM”, available from MacoPharma located in Tourcoing, France.

The storage solution may be contained in a separate storage solution bagthat can be selectively interconnected to the RBC collection bag 954.Such selective interconnection may be provided via sterile-dockingtubing utilizing a sterile connecting device. By way of example, onesuch sterile connecting device to interconnect tubing is that offeredunder the trade name “SCD 312” by Terumo Medical Corporation located inSomerset, N.J. Alternatively, selective interconnection may beestablished utilizing the sterile barrier filter/spike assembly 956. Theuse of assembly 956 facilitates the maintenance of a closed system,thereby effectively avoiding bacterial contamination. By way of example,the mechanical, sterile barrier filter in assembly 956 may include aporous membrane having 0.2 micron pores.

In order to ensure the maintenance of RBC quality, the RBC collectionbag 954, the storage solution and the anticoagulant used during bloodprocessing should be compatible. For example, RBC collection reservoir954 may comprise a standard PVC DEHP reservoir (i.e., polyvinylchloride-diethylhexylphthallate) offered by Medsep Corporation.Alternatively, a citrated PVC reservoir may be employed. Such reservoirmay utilize a plasticizer offered under the trade name “CITRIFLEX B6” byMoreflex located in Commerce, Calif. Further, the anticoagulant utilizedin connection with the above-described platelet collection and red bloodcell collection procedures may be an acid citrate dextrose-formula A(ACD-A).

After the storage solution has been added to the collected red bloodcells in RBC reservoir 954, selective filtering may be desired to removewhite blood cells. More particularly, for example, leukoreduction may bedesired to establish a white blood cell count at <5×10⁸ white bloodcells/unit (e.g., about 250 ml.) to reduce any likelihood of febrilenonhemolytic transfusion reactions. Further, such filtering may bedesirable to achieve a white blood cell count of <5×10⁶ white bloodcells/unit to reduce any risk of HLA (i.e., human leukocyte A)sensitization. If such leukoreduction is deemed appropriate, the redblood cell/storage solution mixture can be connected to a commerciallyavailable red cell filter/bag assembly so that red blood cells aregravity transferred from the collection bag 954 through a filter andinto a new storage bag. Such commercially available red cell filter/bagkits include those available under the trade names “LEUKONET” or “r\LS”from Hemasure, Inc. located in Marlborough, Mass., and “RC 100”, “RC50”and “BPF4” from Pall Corp. located in Glencove, N.Y.

Several advantages can be realized utilizing the above-describedprocedure for red blood cell collection. Such advantages include:consistency in final RBC product volume and hematocrit; reduced exposureof a recipient if multiple units of blood products are collected from asingle donor/patient and transfused to a single recipient; reduced timerequirements for RBC collection and for collection of double units ofred blood cells if desired.

While one approach for platelet and RBC collection has been describedabove, other approaches using the embodiment of FIGS. 2A-2B will beapparent. By way of primary example, the described RBC collectionprocedure may be carried out following blood priming, and prior toplatelet collection. Such an approach would advantageously allow RBCcollection to occur in the course of AC ramping, thereby reducing totalprocessing time requirements. That is, since AC ramping up to apredetermined level (e.g., increasing the AC ratio up to about 13) istypically gradually completed prior to the start of a plateletcollection procedure (e.g., so as to maintain an acceptable ACIR),completing RBC collection procedures in the course of AC ramping wouldreduce the overall processing time for RBC and platelet collection. TheRBC collection procedure could be completed when AC ramping reachesabout 8.14, with AC ramping continuing thereafter. Alternately, RBCcollection could occur in tandem with AC ramping, wherein the target ACratio of about 8.14 would be established as an average effective ratiofor the RBCs and plasma collected and mixed within reservoir 954.

Further, and as noted above, plasma collection could occurcontemporaneous with RBC collection. Additionally, in this regard,plasma collection could occur during both platelet and RBC collectionprocedures, depending upon the volume of plasma product desired.Finally, it has been recognized that the present invention of embodimentof FIGS. 2 a-2 b may also be employable to simultaneously separate andcollect both red blood cells and platelets, and if desired, plasma.

RBC/Plasma (Generally Non-platelet) Collection

As noted, a preferred blood apheresis system 2 also provides forcontinuous separation of red blood cells (RBCs) and plasma with variousalternative collection options. For example, continuous separation maybe provided with contemporaneous collection of both RBCs and plasmaand/or with collection of either RBCs or plasma separately (see, e.g.,the embodiment of FIGS. 2 c-2 d, 8B). In the preferred system, all thenon-collected components are reinfused into the donor. Moreover, theseparated blood components, RBCs and/or plasma (in the embodiments ofFIGS. 2C-2D, e.g.), may be selectively collected, as described above, incorresponding storage reservoirs or immediately returned to thedonor/patient 4 during a blood return/replacement fluid deliverysubmode. Note, the buffy coat components namely platelets and WBCs arenot collected separately in this embodiment (FIGS. 2C-2D). Rather, thesecomponents preferably remain with the RBCs throughout these proceduresand may either be filtered out subsequently, e.g., the WBCs through aleukoreduction filter (e.g., “COBE r\LS” filter) or the like; or mayremain with the RBC product(s) as the platelets likely will, albeitwithout any deleterious effect. Preferably, the plasma product(s) hereofwill remain platelet-poor and contain no WBCs (or at least withinpromulgated minimum safety ranges).

In the present embodiment (FIGS. 2C-2D and 8B), any of three options isprimarily available, the collection of RBCs and plasmacontemporaneously, or RBCs alone, or plasma alone (in either “alone”case, the collection may mean no other product is ever collected duringthat procedure, or no other product is collected at the same time;previous or subsequent collection is also possible). And in one approachwhere both plasma and RBCs are to be collected, blood apheresis system 2may preferably be advantageously employed to collect RBCs and plasmacontemporaneously for a first time period, and then collect eitherplasma or red blood cells for a second period. In this manner, thecollection of both high quality plasma units and high quality red bloodcell units can be realized. Target yields for both components are thusalso preferably achieved or achievable. This may thus include double redblood cell products, for example. Note, a double product quantity ispreferably configurable by the user; however, suggestions have been madefor red blood cell products to be targeted at about 180 or 200milliliters in pure form, which would be 225 or 250 ml at 80 hematocrit(i.e., including 20% plasma in the end product). Thus, a double RBCproduct under these suggestions would be about 360 or about 400 ml. inpure form and 450 to 500 at 80 hematocrit. Note, the 180 ml. suggestionmay be based upon an understood concept of a whole blood donation unitof 450 ml.+10% which would provide about 60 grams of hemoglobin (Hb) oran average 180 ml. hematocrit (Ht) (see U.S. Federal Food and DrugAdministration (FDA) suggestions). Other sizes can also be configuredand collected based upon donor ability.

Replacement fluid(s) are preferably also optionally administrable withinthe procedures of the present invention using the embodiment of FIGS.2C-2D. Sterile saline solution(s) and/or replacement/exchange plasma(and/or replacement/exchange red blood cells) are optional replacementfluids, inter alia, considered for use herein. Thus, if/when large fluidamounts of plasma and/or RBCs are taken from a donor/patient,replacement fluid(s) may be delivered in return to leave thedonor/patient adequately hydrated i.e., replacement fluids may, incertain situations, qualify more product options from a given donor. Forexample, a particular donor may not qualify for a certain donation(e.g., a double RBC product) under normal conditions; however, with areplacement fluid infusion, that donor may then qualify for thatdonation.

Also, replacement fluids may also be used to avoid hypovolemia and likereactions. Bolus deliveries are also preferably deliverable herewithin.Exchange fluids (plasma and/or RBCs) may be used for therapeuticpurposes as well. These alternatives are detailed further hereinbelow.Note first however that it is preferable that the one or morereplacement fluid spike assembly(ies) 964 (964 a/964 b) are/may besimilar structurally and/or functionally to the anticoagulant spikeassembly 50/52 shown and described hereinabove; but it is preferablethat there be some distinction therefor safety reasons. For example, ifa plastic spike is used for the anticoagulant line(s), it would then bepreferable to include a metal or distinctly colored or shaped spike orspikes for the replacement fluid line(s) so that the operator will notconfuse them and accidentally run anticoagulant into the replacementfluid system and thereby potentially seriously overload thedonor/patient with anticoagulant.

The general set-up or initiation procedures described hereinabove forany and/or all other apheresis procedures are likewise and/or similarlycarried out here to provide blood priming of extracorporeal tubingcircuit 10 a (FIGS. 2C-2D) and blood processing vessel 352 a (FIG. 8B)(distinctions are described herein). The initiation of blood processingthereafter then provides for the collection of plasma in one or morereservoir(s) 94 and/or the collection of red blood cells in one or morereservoir(s) 954. Alternatively, either RBC collection in reservoir(s)954 or plasma collection in reservoir(s) 94 may also be selectivelycompleted in separate procedures. During either collection procedure,blood component separation device 6 preferably controls the initiationand termination of successive blood removal and blood return submodes,as described for example, in the preferred embodiment hereinabove (fromand to the donor through level control in the cassette reservoir 150using the two ultrasound fluid level detectors 1300, 1320, e.g.).Additionally, blood component separation device 6 will control theplasma and RBC collection processes according to predeterminedprotocols, preferably including control over the preferred valveassemblies 1100, 1110 and 1120 of the pump/valve/sensor assembly 1000,and/or the appropriate pumps 1020, 1030, 1040, 1060 and/or 1090.

Initially, blood priming is carried out generally as describedhereinabove. However, as described here, a further step during primingis preferably instituted prior to starting component collection. Duringblood priming, it is still desirable that the component separation begineven during the priming stage, and that plasma flows over the RBC dam232 and continues around to the plasma outlet port 456 and still furtheraround to the RBC/control outlet 520 (see FIG. 8B); while RBCs build upbehind the RBC dam 232 and flow in a counterflow direction back to theRBC/control outlet 520. (Note that the buffy coat elements preferablyremain behind the dam 232 as well and flow to the RBC outlet port 520with the RBCs; however, even though not preferred, sufficientfunctionality may nevertheless likely be retained even if some RBCsand/or buffy coat components flow over the dam 232 during priming.Potential WBC contamination of platelet collection apparatus is not herein issue, though it may be an issue for the plasma collection assembly,as well). The further priming step here is to then shut the plasma pump1060 off for a period and thereby force a greater quantity of separatedplasma toward the RBC/control outlet portand thereby force the highhematocrit separated RBCs out of the vessel 352 a through theRBC/control outlet 520 until the plasma/RBC interface moves radiallyoutward toward the orifice 536 of the outlet port 520. Eventually,plasma reaches the orifice 536 and spills thereinto and flows outthrough the outlet port 520. This plasma spilling into port 520 suggestsit may also be called a spill port 520. Note, a greater quantity ofplasma also fills the first stage 312 thus also contributing to theforcing of the RBC/plasma interface radially outward. Then, when theinterface is established at or sufficiently adjacent the RBC orifice536, as preferred here, the plasma pump may be automatically turned backon by the separation device 6 at a rate which maintains the RBC/plasmainterface at or sufficiently adjacent the radial level of theRBC/control outlet orifice 536. In particular, it is desirable that theinterface be maintained at this location such that a mixed flow of RBCsand plasma is maintained continuously through the RBC/control outletport 520 such that the mixed flow of RBCs and plasma has reached andcontinues at a target hematocrit, here preferably at about 80.Maintenance by the device 6 of a particular relationship of the rate ofplasma outflow generated by the plasma pump 1060 relative to the inletrate of blood flow generated by the blood inlet pump 1030 provides forcontinuing the target output hematocrit of the RBC/plasma mixed flowthrough the RBC/control outlet port 520.

Following and/or contemporaneously with the blood priming phase asdescribed hereinabove, blood separation control device 6 providescontrol signals to pump/valve/sensor assembly 1000 so that thereplacement fluid lines may also be primed. In particular, replacementfluid valve assembly 1100 is opened and replacement fluid inlet pump1040 is switched on to provide for the pumping of saline solution (orother replacement fluid(s)) through replacement fluid inlet tubing 962and the replacement fluid tubing loop 142 a into replacement fluidintroduction tubing line 146 for initial collection in cassettereservoir 150, though this initial priming collection will likely andpreferably does constitute a small amount of replacement fluid(s).

After priming is completed, yet still during the set-up phase, bloodcomponent separation device 6 may provide appropriate control signals tothe pump/valve/sensor assembly 1000 such that all separated bloodcomponents flowing out of processing vessel 352 a will first pass toreturn/delivery reservoir 150. Optionally, one or more cycles(preferably two) of separation and return of all blood components backto the donor may be performed before collection(s) and/or regularreplacement fluid deliveries begin (this may be performed in order tostabilize the hematocrit in the first stage of vessel 352 a). Anyreplacement fluid(s) collected in reservoir 150 during priming (again,likely very small amounts) may also be delivered to the donor/patient atthis time. Also, blood component separation device 6 may continueoperation of blood inlet pump assembly 1030 during one or more theseinitial blood component return submodes.

Then, the process of collection may begin. If plasma collection is notdesired, plasma divert assembly 1110 maintains the flow of separatedplasma from the vessel 352 a to the reservoir 150 for return to thedonor/patient 4. However, if plasma collection is desired (either aloneor contemporaneously with RBCs), blood component separation device 6 mayprovide control signals so that plasma divert valve assembly 1110switches to divert the flow of separated plasma pumped from vessel 352 athrough plasma outlet tubing 68 and plasma tubing loop 162 into plasmacollector tubing 92 for collection in one or more plasma reservoir(s)94. Additionally, if plasma is to be collected alone, RBC divert valveassembly 1120 will continue to maintain the flow of separated RBCsflowing from vessel 352 a through outlet tubing 64 through return tubingloop 172 and into blood return reservoir 150. However, if RBCs are to becollected, alone or contemporaneously with plasma, then the RBC divertvalve assembly 1120 switches to divert the flow of separated RBCsflowing from tubing 64 to and through spur 170 b (of cassette 110) andinto and through tubing line 952 to the one or more RBC collectionreservoir(s) 954. No platelet collection is preferably carried out inthis embodiment as previously discussed hereinabove.

Preferably during any of the collection processes involved with thisembodiment (FIGS. 2C-2D), one or more replacement fluid(s) are alsodelivered to the donor/patient 4. Thus, whenever either divert valveassembly 1110 or 1120 is switched by the separation device 6 into acollection mode, then the replacement fluid inlet valve assembly 1100may also be opened and the replacement fluid pump 1040 started to flowreplacement fluids from the fluid source (not shown) through tubing line962, cassette passageways 140 c and 140 d, and tubing loops 142 a and146 into the reservoir 150 (FIGS. 2C-2D). As a basic premise, thereplacement fluid flow rate is equal to the total collection flow ratemultiplied by the percentage of fluid desired to be given back to thedonor/patient 4. This last factor is called a fluid balance percentage.Preferably, the rate of replacement fluid flow (Q_(rf)) is governed bythe relationship of the total collection flow rate (Q_(tot)) minus theflow rate of the anticoagulant inflow (Q_(ac)) multiplied by the totalfluid balance percentage (FB) ultimately delivered back to thedonor/patient 4. In mathematical form;Q _(rf) =[Q _(tot) −Q _(ac) ]*FB;

Preferably, the fluid balance percentage is chosen within a limitedrange of 80% and(e.g., 80% representing the lessened amount of fluid thedonor/patient 4 is given back, or has received at the end of theprocedure relative to the donor/patient's donation amount, and 120%representing the additional amount of fluid given to the donor/patient 4over the donation amount; thus, if 80% is chosen for example, then thedonor/patient 4 ends the procedure with 80% of the donated fluidvolume).

Note, a further option of fluid bolus infusion may be offered with areplacement fluid assembly such as that described herein. For example, aprocedure for bolus infusion may be made available at any desired pointin a procedure. As such, it may involve stopping all pumps except atleast the replacement fluid inlet pump 1040 which delivers replacementfluid to the reservoir 150 at a selected infusion rate, then (withperhaps a slight delay to ensure a minimum level of fluid is present inthe reservoir 150 prior to fluid return/delivery to the donor/patient),the return/delivery pump 1090 may be started to deliver the replacementfluid from the reservoir 150 to the donor/patient 4. A bolus button forinitiating such a procedure may be permanently disposed on theseparation device 6, and/or it may preferably be disposed on one or moreselected touch screen(s) (see generally below) which may be displayed onthe computer graphical interface 660. This may appear on an adjustmentor troubleshooting screen, for example (see description(s) below).

When RBCs are collected contemporaneously with plasma, a packing factorin the first stage of vessel 352 a is maintained preferably at 16. IfRBCs are collected alone, then the packing factor is set between about 4and 15, more preferably between 11 and 15, and most preferably at about13. When the desired volumes of RBCs and/or plasma have been collected,blood component separation device 6 will preferably selectively controldivert assemblies 1110 and 1120 to divert the respective flow of RBCsand/or plasma (whichever has reached its desired collected volume) intoreservoir 150.

Following contemporaneous RBC and plasma collection (if this procedureis chosen), at which point either the target RBC volume/yield or thetarget plasma volume/yield (or both) has been reached, then therespective divert valve assembly 1110 or 1120 (or both) of therespective component whose target volume/yield has been reached isswitched to divert flow of that separated component to flow to thereservoir Thus, if and when the target volume/yield of RBCs has beenreached, then the divert valve assembly 1120 may be switched to returnflow of separated RBCs to the reservoir 150, independent of and/or evenif the plasma target volume/yield has not yet been reached. The same maybe true in reverse, if and when the plasma target volume/yield has beenreached, even if this occurs before the RBC target is reached, then theplasma divert valve assembly 1110 may be switched to flow the stillincoming separated plasma to the reservoir 150. Then, collection of theother component is preferably continued until its target volume/yield isreached. Note, though either separated component may be collected first,and then the other components collected after the target volume/yield ofthe first component has been reached, it is preferable to start theprocedure collecting both RBCs and plasma contemporaneously (assumingthat a quantity of both products are desired from a given donor), andthen switch to collecting only the component whose target volume/yieldhas not yet been reached when the other target has been reached.

Control over these switching steps after achieving either the RBC or theplasma target collection volumes/yields is initiated via control signalsprovided by blood collection/separation device 6 to the respectivedivert valve assemblies 1110 and 1120. Note also that the separationdevice 6 may make further adjustments as well upon switching from thecontemporaneous collection of RBCs and plasma to the collection of onlyone such component. For example, the packing factor has been noted aspreferably kept at 16 with a target hematocrit of 80 during collectionof both RBCs and plasma contemporaneously. However, when the targetvolume/yield of one or the other blood component has been reached andthen collection of only one component is continued, then the separationdevice 6 preferably adjusts to the preferred packing factor orhematocrit value as discussed herein. Specifically, if the plasma targethas been reached, but RBC collection is to continue, the separationdevice preferably lowers the packing factor to the range disclosedherein, preferably to 11-15, or set even more preferably at 13 whilemaintaining a target hematocrit of 80. If, on the other hand, collectionof plasma is instead to be continued after the target for RBCs has beenreached, then the separation device 6 may reset the target hematocrit toapproximately 55, for example, without concern for the resulting oractually occurring packing factor at this point.

Such RBC and/or plasma collection procedures may also include a setupphase and a collection phase. During a setup phase, the blood apheresissystem 2 may be adjusted to establish a predetermined hematocrit inthose portions of the blood processing vessel 352 a and extracorporealtubing circuit 10 a through which separated RBCs will pass forcollection during the RBC collection phase. More particularly, duringthe setup phase, and in order to realize a predetermined hematocrit ofabout 80%, the packing factor in the first stage 312 of the bloodprocessing vessel 352 a is established at between about 11 and about 21,and most preferably at about 16 for contemporaneous RBC and plasmacollections, or 13 for RBC collections, alone. These are the preferredpacking factors for collection phases of RBCs and plasma simultaneously,and RBCs alone, see discussions throughout. Additionally, the AC ratio(i.e., the ratio between the inlet flow rate to vessel 352 a (includingwhole blood plus anticoagulant AC) and the AC flow rate into tubingcircuit 10) will be established within the range of about 6 to 16, andmost preferably at about 8.14 (in the United States) and/or 11 (in othercountries). Further, the total uncollected plasma flow rate throughblood processing vessel 352 a and extracorporeal tubing circuit 10 maybe established at a predetermined level. These adjustments arepreferably carried out by controlling the speeds of the respective pumpsand/or the centrifuge which may be adjusted in simultaneous fashion toestablish the desired hematocrit in an expeditious manner. As will beappreciated, this adjusted AC ratio and predetermined hematocrit shouldbe maintained during the subsequent RBC and plasma collection phase(s).

These adjustments will not affect the other collection controlparameters where again, when collecting RBCs alone, the targethematocrit remains at 80, but the packing factor is preferably reducedto, for example, 11-13. This is similar to the RBC packing factorpreference described above for the collection phase of RBCs afterplatelet collection has ceased (for the platelet/plasma/RBC embodiment;e.g., FIGS. 2A-2B, and corresponding description, above). Further still,when collecting plasma alone, the target hematocrit is preferablydropped to 55, and the packing factor in the first stage is not an issue(also as described hereinabove).

In order to establish the desired packing factor, the operating speed ofcentrifuge rotor assembly 568 may be selectively established via controlsignals from blood component separation device 6, and/or the blood inletflow rate to vessel 352 a may be selectively controlled via control byblood component separation device 6 over pump assembly 1030, and/or theplasma flow rate out through port 456 may similarly be controlled bydevice 6 through pump 1060. More particularly, increasing the rpms ofcentrifuge rotor assembly 568 and/or decreasing the inlet flow rate willtend to increase the packing factor, while decreasing the rpms and/orincreasing the flow rate will tend to decrease the packing factor. Ascan be appreciated, the blood inlet flow rate to vessel 352 a iseffectively limited by the desired packing factor.

To establish the desired AC ratio, blood component separation device 6provides appropriate control signals to anticoagulant peristaltic pump1020 so as to introduce anticoagulant into the blood inlet flow at apredetermined rate, as previously described hereinabove. Relatedly, inthis regard, it should be noted that the inlet flow rate ofanticoagulated blood to blood processing vessel 352 a is limited by apredetermined, maximum acceptable anticoagulant infusion rate (ACIR) tothe donor/patient 4. As will be appreciated by those skilled in the art,the predetermined ACIR may be established on a donor/patient-specificbasis (e.g., to account for the particular total blood volume of thedonor/patient 4).

To establish the desired total uncollected plasma flow rate out of bloodprocessing vessel 352 a, it should be noted that when RBCs and plasmaare collected simultaneously/contemporaneously, there is no uncollectedplasma. Further, when plasma is collected alone, the uncollected plasmais that portion of the RBC/plasma outflow (i.e., that plasma flowing outRBC outlet port 520 with the RBC's through line 64) which may bedetermined by the hematocrit thereof. With a target hematocrit of about55 in RBC line 64 during plasma collection alone, the uncollected plasmawill constitute about 45% of that outflow. In either event, the bloodcollection device 6 provides appropriate control signals to plasma pumpassembly 1060 to establish the desired total plasma flow rate,uncollected or collected. Relative to RBC collection, on the other hand,such control signals will typically serve to increase plasma flowthrough plasma outlet port 456, and thereby reduce plasma flow with RBCsthrough RBC outlet port 520. This serves to increase the hematocrit inthe separated RBCs, to the target hematocrit of 80.

In one embodiment, where centrifuge rotor assembly 568 defines a rotordiameter of about 10 inches, and where a blood processing vessel 352 a(see FIGS. 2C-2D and 8B) is utilized, as described hereinabove, it hasbeen determined that channel housing 204 can be typically driven at arotational velocity of about 3000 rpms to achieve the desired hematocritduring the both the setup and component collection phases.Correspondingly, the blood inlet flow rate to vessel 352 a shouldpreferably be established at below about 64.7 ml/min. The desiredhematocrit can be reliably stabilized by passing about two whole bloodvolumes of vessel 352 a through vessel 352 a before the RBC and/orplasma collection phases are initiated.

To initiate an RBC collection phase, blood component separation device 6pro an appropriate control signal to RBC divert valve assembly 1120 soas to direct the flow of RBCs removed from blood processing vessel 352 ainto RBC collection reservoir In an RBC only collection, plasma divertvalve assembly 1110 remains in a position to direct flow into reservoir150 for return of the separated plasma to donor/patient 4 during bloodreturn/replacement fluid delivery submodes. Upon and/or simultaneouslywith initiation of RBC collection, replacement fluid valve assembly 1100also preferably is switched to provide replacement fluid flow also intothe reservoir 150. In all RBC collection and/or replacement fluidoperational phases, it is preferable that, during blood componentreturn/replacement fluid delivery submodes of the RBC collection phase,blood collection and separation device 6 provides appropriate controlsignals so as to stop the operation of all pump assemblies other thanreturn/delivery pump assembly 1090. In this regard, stoppage of inletpump assembly 1030 avoids recirculation of uncollected blood componentsand/or replacement fluid(s) into vessel 352 a and resultant dilution ofseparated RBC components within vessel 352 a.

As will be appreciated, and as was also true in the previously describedabove, in the present invention separated RBCs are not pumpedpost-separation out of vessel 352 a through line 64 for collection, butinstead are moved out of vessel 352 a and through extracorporeal tubingcircuit 10 a by the relative pressure of the blood inlet flow to vessel352 a (as this may be modified by the plasma outlet pressure through theplasma outlet port 456). Consequently, trauma to the separated andcollected RBCs is minimized.

During the RBC and/or plasma collection phases, the inlet flow intovessel 352 a is limited as described above by the above-noted maximumacceptable ACIR to the donor/patient 4. The desired inlet flow rate isalso limited by that necessary to maintain the desired packing factor,as also discussed. In this regard, it will be appreciated that, relativeto the setup phase, the inlet flow rate may be adjusted slightly upwardsduring the RBC and/or plasma collection phases since not allanticoagulant is being returned to the donor/patient 4. That is, aportion of the anticoagulant remains with the collected plasma and/orthe plasma that is collected with the RBCs in RBC reservoir(s) 954.

Following collection of the desired quantity of red blood cells and orplasma, and after blood separation device 6 has provided control signalsto divert assemblies 1110 and so as to divert the respective separatedplasma and separated RBC flows to reservoir 150, if further bloodprocessing is not desired, rinseback procedures may then be completed asgenerally described above. However, here (in the embodiment of FIGS. 2c-2 d) where there is no platelet pump splitting the rinseback flow, theplasma pump 1060 is set at the full plasma rate equal to rate of thereturn/delivery pump 1090 for rinseback. Note again, that thereplacement fluid inlet pump 1040 is stopped here also as in all(non-bolus) instances when no RBCs or plasma are being collected.

Additionally, at the end of the procedures, the plasma bag(s) 94 and thered blood cell reservoir(s) 954 may be disconnected from theextracorporeal tubing circuit 10 in fashions like those described above.Storage solutions may also be added, also as described above.Post-collection filtration may also be performed. For example,leukoreduction/white blood cell filtration from the collected RBCs in afashion as described above, before or after the option of adding astorage solution. The storage solutions and/or filtration devices andcorresponding final storage reservoir(s) (not shown) may, as describedhereinabove, be preconnected to the collection reservoirs herein, orattached subsequently via sterile connection or spike and sterilebarrier connections, also as described hereinabove.

Note, a further beneficial feature of the present invention is that itis preferred that the system 2 be able to monitor or model thehematocrit (and/or platelet count) and the total blood volume of thedonor/patient 4 during the overall procedure. For example, the machine 6can continuously and instantaneously monitor the quantity of RBCscollected, the plasma collected, the anticoagulant (AC) collected witheither or both the RBCs and/or plasma as well as the AC delivered to thedonor/patient 4, and, if used, the saline/replacement solution deliveredto the donor/patient 4 to determine the instantaneous hematocrit (and/orplatelet count and/or the total blood volume) of the donor/patient 4. Iffor example, a donor started with a 45 hematocrit and a total bloodvolume of 5 liters (roughly equivalent to about 2.25 liters of RBCs),and the equivalent of 0.5 liters of whole blood were removed, and say a0.5 liters of replacement fluid were added, then a result would be 2.02liters of RBCs with a total blood volume of 5 liters and a resultinghematocrit of 40. Most desirably, this drop of hematocrit during aprocedure may be instantaneously modeled so that the target hematocritof the resulting products can continue to met. This may mean adjustmentsto certain flow rates such as the plasma pump rate to ensure that thetarget amount of separated plasma reaches and exits with the RBCsthrough the RBC exit port to provide the target hematocrit. Double redblood cell products and/or replacement fluid options will have greaterimpact on and/or be more greatly impacted by the instantaneoushematocrit of the donor/patient. Thus, this modeling provides betterinsurance that the target hematocrit will be reached even in a doublered blood cell product.

Note further that instantaneous platelet and/or total blood volumemonitoring may also be performed in similar fashions, and can also beused to ensure the quality of the platelet and/or plasma products byfeed back adjustment control over certain flow rates. Moreover, theseand similar procedures may be used to mode for ending or posthematocrit, platelet count and/or total blood volumes as protectionmeasures for the donor/patient. For example, an ending total bloodvolume (or instantaneous such volume) may be pre-set as a maximumremoval from the body in total (or at any time during the procedure);then, the machine 6 will be pre-disposed to disallow the start of anyprocedures (or stop a progressing procedure) which would ever remove intotal (or at anytime during a procedure) any amount more than thispre-set maximum. An example maximum might be 15% of the donor's startingtotal volume (calculated preferably using height and weight). A usercould choose other percentage options as well, as for example a moreconservative 13%, inter alia. Similarly, post hematocrit and plateletpost-count limits may also be pre-set (or configurable per each donor).Examples might be 30 or 32 post hematocrits, and/or 50,000 or 100,000platelet post-counts. Maximum procedure times might also be used in suchdonor safety areas; e.g., 120 or 150 minute maximum procedure times.

As above, several advantages can be realized utilizing these proceduresfor red blood cell and/or plasma collections. Such advantages include:consistency in final RBC product volume and hematocrit; reduced exposureof a recipient if multiple units of blood products are collected from asingle donor/patient and transfused to a single recipient; reduced timerequirements for RBC and/or plasma collections and for collection ofdouble units of red blood cells if desired.

Various approaches for plasma and RBC collection have been describedabove, and other approaches may also be beneficial. By way of anexample, the described RBC collection procedure may be carried outfollowing blood priming, but prior to plasma collection. Such anapproach may advantageously allow RBC collection to occur in the courseof AC ramping, thereby perhaps reducing total processing timerequirements. That is, since AC ramping up to a predetermined level(e.g., increasing the AC ratio up to about 13), may be graduallycompleted prior to the start of a plasma collection procedure (e.g., soas to maintain an acceptable ACIR), completing RBC collection proceduresin the course of AC ramping may reduce the overall processing time forboth RBC and plasma collection. The RBC collection procedure could becompleted when AC ramping reaches about 8.14 (in the U.S.) or 11 (inother countries), with AC ramping continuing thereafter. Alternatively,RBC collection could occur in tandem with AC ramping, wherein the targetAC ratio of about 8.14 or 11 would be established as an averageeffective ratio for the RBCs and plasma collected and mixed withinreservoir(s) 954.

Further alternative procedures are available, for example in therapeuticexchanges of RBCs or plasma, such that the exchange RBCs or plasma isthe replacement fluid to be delivered through the replacement fluidtubing assembly 960 to the donor/patient 4 while the corresponding RBCsor plasma is removed from the donor/patient as described hereinabove.Collected components may similarly be therapeutically treated uponcollection and then returned to the patient through the replacementfluid tubing assembly 960.

Alternative Collections

As mentioned, the present invention provides for the selection ofvarious alternative component products to be collected. At least twodiscrete tubing and processing vessel sets have been described toachieve these options. The primary advantage is that any of these andother options may be obtained on the same platform or system. Forexample, extracorporeal blood processing system 2 (see generally FIG. 1)may be used to separate blood in various components and provide for theselection of collections of platelets (single, double or tripleproducts, e.g.), alone or in combination with other products such asRBCs (single or double) and/or plasma (various quantities). Moredirectly, given a particular donor ability (through blood volume,hematocrit and platelet count, e.g.), an operator of the present systemmay be presented with various options of donation combinations. Then,the operator may choose the most desirable option, and load theappropriate tubing set (see e.g., FIGS. 2A-2B vs. 2C-2D) on the machine6, and then collect the desired component products. The system 2/machine6 would operate the appropriate protocols as described hereinabove.

Note, other options are foreseeable as well. For example, though notexplicitly shown above (not as preferred), platelets could be collectedon a tubing set having a replacement fluid option such as that describedrelative to FIGS. 2C-2D. However, the vessel would be like vessel 325(FIGS. 2A-2B, with the platelet outlet line running to and through theplasma pump 1060, e.g.) and the protocol preferably as described for theRBC/platelet option above (preferably platelet collection first, withRBCs to follow). Or, such a platelet/RBC with replacement fluids optioncould be formed of the tubing set of FIGS. 2A-2B with the replacementfluids run through the plasma pump 1060 with no plasma collectionreservoirs then available. The limiting factor in the shown system is afurther pump. In other words, if a further pump were added (not shown)to the machine 6, then a platelet/plasma/RBC tubing set such as thatshown in FIGS. 2A-2B could be used with an additional pump and tubingline set running to and through the added pump to flow to the reservoir150. A further limiting factor is that during platelet collections,replacement fluids are generally not necessary. Larger collections, suchas double red blood cell products more often indicate a desirability forreplacement fluids. Along this line, a further red blood cell containercould be added to the tubing set of FIGS. 2A-2B; however, again, thepreference would be to have a replacement fluid option available (thoughnot necessary in all cases) for double red blood cell collections.

In either case, substantially all practical options are presentlyavailable using the two tubing sets shown and described herein.Moreover, other sets are also available, as for example aplatelet/plasma set such as is shown and described in U.S. Pat. No.5,653,887 to Wahl et al.; inter alia (assigned to the assignee of thepresent document). Such sets (as described therein) may also be usedwith the system of the present invention, and provide a further optionto the users hereof.

Graphical Computer Interface

In order to assist an operator in performing the various steps of theprotocol being used in an apheresis procedure with the apheresis system2, the apheresis system 2 further includes a computer graphicalinterface 660 illustrated in FIG. 1. The following descripdescribes aninterface for use by an English language speaking operator. For otheroperations and/or languages, the textual portions of the interfacewould, of course, be adapted accordingly. The graphical interface 660includes a computer display 664 which has “touch screen” capabilities.Other appropriate input devices (e.g., keyboard) may also be utilizedalone or in combination the touch screen. For example, a pump pause anda centrifuge stop button of the well known membrane type may beprovided. The graphics interface 660 not only allows the operator toprovide the necessary input to the apheresis system 2 such that theparameters associated with operation of the apheresis system may bedetermined (e.g., data entry to allow determination of various controlparameters associated with the operation of the apheresis system 2), butthe interface 660 also assists the operator by providing pictorials ofat least certain steps of the apheresis procedure. Moreover, theinterface 660 also effectively conveys the status of the apheresisprocedure to the operator. Furthermore, the interface 660 also may beused to activate standardized corrective actions (i.e., such that theoperator need only identify the problem and indicate the same to theinterface 660 which will then direct the apheresis system 2 to correctthe same).

Referring to FIG. 26, at the start of an apheresis procedure a masterscreen 696 is displayed to the operator on the display 664. The masterscreen 696, as well as each of the screens displayed to the operator bythe interface 600, includes a status bar 676. The status bar 676includes a system prep icon set 700. The system prep icon set 700includes a load icon 704 (representing the shape of blood componentseparation device 6) with a downwardly extending arrow whichcollectively pictorially conveys to the operator that the disposable set8 must be loaded onto the blood component separation device 6. The word“LOAD” is also positioned below the load icon 704 to provide a shorttextual instruction to the operator of the required action(s).

The system prep icon set 700 also includes an information icon 708(representing the shape of an open filing folder) which pictoriallyconveys to the operator that certain information relating to thedonor/patient 4, the procedure protocol, and/or the blood componentseparation device 6 must be obtained and entered. This information maybe utilized by the apheresis system 2 to calculate one or more of theparameters associated with the apheresis procedure (e.g., inlet flowrate to the blood processing vessel 352) and/or to generate predictedyields of one or more blood component types (e.g., the amount of acertain blood component type which is anticipated to be collected basedupon certain parameters such as donation time). The word “INFO” is alsopositioned below the information icon 708 to provide a short textualinstruction to the operator of the required action(s). The informationicon 708 is also positioned to the right of the load icon 704 toindicate to the operator that it is preferred, although not required, toperform the step(s) associated with the information icon 708 after thestep(s) associated with the load icon 704 have been completed.

The status bar 676 also includes a collection icon set 712. Thecollection icon set 712 includes a donor/patient prep icon 716(representing the shape of the donor/patient 4) which pictoriallyconveys to the operator that the donor/patient 4 must now be fluidlyinterconnected with the blood component separation device 6. The word“PRE-PARE” is also positioned below the donor/patient prep icon 716 toprovide a short textual instruction to the operator of the requiredaction(s). The donor/patient prep icon 716 is also positioned to theright of the information icon 708 to indicate to the operator that thestep(s) associated with the donor/patient prep icon 716 may only beperformed after the step(s) associated with the load icon 704 and theinformation icon 708 have been completed.

The collection icon set 712 also includes a donate icon 720 with alaterally extending arrow which collectively pictorially conveys to theoperator that the actual collection procedure may be initiated and thatthe step(s) to initiate this action should now be performed. The word“DONATE” is also positioned below the donate icon 720 to provide a shorttextual instruction to the operator of the required action(s). Thedonate prep icon 720 is also positioned to the right of thedonor/patient prep icon 716 to indicate to the operator that the step(s)associated with the donate icon 720 must be performed after the step(s)associated with the donor/patient prep icon 716 have been completed.

The status bar 676 also includes an unload icon 724 (representing theshape of the blood component separation device 6) and a generallyupwardly extending arrow which collectively pictorially convey to theoperator that the disposable set must now be removed from the bloodcomponent separation device 6. The word “UNLOAD” is also positionedbelow the unload icon 724 to provide a short textual instruction to theoperator of the required action(s). The unload icon 724 is alsopositioned to the right of the donate icon 720 to indicate to theoperator that the step(s) associated with the unload icon 724 must beperformed after the step(s) associated with the donate icon 720 havebeen completed.

The system preparation icon set 700, collection icon set 712, and unloadicon 724 in the status bar 676 sequentially set forth certain basicsteps for the apheresis procedure. That is, the left to rightpositioning of the various icons conveys to the operator thedesired/required order in which the step(s) associated with the iconsshould/must be performed. Moreover, the individual icons 704, 708, 716,720, and 724 are also utilized to convey the status of the apheresisprocedure to the operator via three-way color differentiation (i.e., onestatus per color) and/or by three-way shade differentiation. “Shades”includes variations of a given color and also encompasses usingvariations based upon being “lighter” and/or “darker” (e.g., using lightgray, medium gray, and dark gray). That is, a “gray-scale” technique mayalso be utilized and is encompassed by use of color and/or shadedifferentiation.

The first status conveyed to the operator by the icons in the status bar676 is that the step(s) associated with respective icon are not ready tobe performed. That is, the performance of this step(s) would bepremature. This first status is conveyed to the operator by displayingthe associated icon in a first color, such as white. The correspondingtextual description may also be presented in this first color as well.As noted, a first “shade” may also be utilized to convey this firststatus as well.

The second status conveyed to the operator by the icons in the statusbar 676 is that the step(s) associated with the respective icon iseither ready for execution or is in fact currently being executed. Thatis, an indication is provided to the operator that performance of thisstep(s) of the apheresis procedure is now timely. This second status isconveyed to the operator by displaying the associated icon in a secondcolor, such as yellow. The corresponding textual description may also bepresented in this second color as well. As noted, second “shade” mayalso be utilized to convey this second status as well.

The third status conveyed to the operator by the icons in the status bar676 is that the step(s) associated with the respective icon has beenexecuted. That is, an indication is provided to the operator thatperformance of this step(s) of the apheresis procedure has beencompleted.

This third status is conveyed to the operator by displaying theassociated icon in a third color, such as gray. The correspondingtextual description may also be presented in this third color as well.As noted, third “shade” may also be utilized to convey this third statusas well.

Based upon the foregoing, it will be appreciated that significantinformation is conveyed to the operator by merely viewing the status bar676. For instance, the operator is provided with a pictorial graphicindicative of the fundamental steps of an apheresis procedure. Moreover,the operator is provided with a textual graphic indicative of thefundamental steps of an apheresis procedure. Furthermore, the operatoris provided with a desired/required order in which these stepsshould/must be performed. Finally, the operator is provided with thestatus of the apheresis procedure via the noted three-way color/shadedifferentiation.

The master screen 696, as well all other screens displayed to theoperator by the interface 660 during an apheresis procedure, alsoinclude a work area 688. The work area 688 provides multiple functions.Initially, the work area 688 displays additional information(pictorially and textually in some instances) on performing theapheresis procedure to the operator (e.g., certain additional substepsof the apheresis procedure, addressing certain “conditions” encounteredduring the apheresis procedure). Moreover, the work area 688 alsodisplays additional information on the status of the apheresis procedureto the operator. Furthermore, the work area 688 also provides foroperator interaction with the computer interface 660, such as byallowing/requiring the operator to input certain information.

Continuing to refer to FIG. 26, the work area 688 of the master screen696 displays a load system button 728 and a donor/patient info button780. The operator may touch either of these buttons 728, 780 (i.e.,since the display 696 has “touch screen” capabilities) to generatefurther screens for providing information to the operator and/or tofacilitate the inputting of information to the computer interface 660.The operator may initially touch either the load system button 728 orthe donor/patient info button 780 at the start of an apheresisprocedure. That is, the order in which the step(s) associated with theload system button 728 are performed in relation to the apheresisstep(s) associated with the donor/patient info button 780 are performedis not generally important (i.e., the steps associated with the loadsystem button 728 may be performed before or after the steps associatedwith the donor/patient info button 780). The apheresis procedure will bedescribed with regard to the operator electing to initially activate theload system button 728 via the touch screen feature.

However, as described below, it has become more preferable to performthe donor/patient information step(s) before loading the disposableassembly because alternative disposable assemblies are now available(see e.g., the alternative forms of cassette and vessel assemblies inFIGS. 2A, 2B relative to those of FIGS. 2C, 2D. Thus, by performing thedonor information step (FIGS. 32-46, below) first, a selection of whichcassette and/or vessel assembly (e.g., vessel 325 or 325 a of respectiveFIGS. 2A, 2B or 2C, 2D) might be preferred for a given donor. Thisoption will be described further below.

Whether before or after donor information has been entered (seedescription of FIGS. 32-46, below), activation of the load system button728 generates a loading procedure screen 732 on the computer display 664which is illustrated in FIG. 27. The loading procedure screen 732displays multiple pictorials to the operator in the work area 688 whichrelate to the steps which need to be performed to prepare the bloodcomponent separation device 6 for an apheresis procedure. Initially, ahang pictorial 736 is displayed which pictorially conveys to theoperator that the various bags (e.g., an AC bag(s) (not shown), plasmacollect bag(s) 94 platelet collect bag(s) 84) need to be hung on theblood component separation device 6 and generally how this step may beaffected by the operator. The word “HANG” is also positioned above thehang pictorial 736 to provide a short textual instruction to theoperator of the required action(s). Consequently, there are twodifferent types of graphical representations provided to the operatorrelating to a specific operator action which is required to prepare theblood component separation device 6 for the apheresis procedure.Moreover, the hang pictorial 736 is disposed on the left side of theloading procedure screen 732 which indicates that this is the first stepor substep associated with the load icon 704. In order to providefurther indications of the desired order to the operator, the number “1”is also disposed adjacent to the word “HANG.”

A focus color (e.g., yellow) or shade may be used to direct theoperator's attention to specific areas of the machine or screen. Theloading procedure screen 732 also displays an insert pictorial 740 tothe operator in the work area 688. The insert pictorial 740 pictoriallyconveys to the operator that the cassette assembly 110 needs to bemounted on the pump/valve/sensor assembly 1000 of the blood componentseparation device 6 and generally how this step may be affected by theoperator. The word “INSERT” is also positioned above the insertpictorial 740 to provide a short textual instruction to the operator ofthe required action(s). The insert pictorial 740 is also positioned tothe right of the hang pictorial 736 to indicate to the operator that itis preferred, although not required, to perform the step(s) associatedwith the insert pictorial 740 after the step(s) associated with the hangpictorial 736 have been completed. In order to provide furtherindications of the desired order to the operator, the number “2” is alsodisposed adjacent to the word “INSERT.” The loading procedure screen 732also displays a load pictorial 744 to the operator in the work area 688.The load pictorial 744 pictorially conveys to the operator that theblood processing vessel 352 needs to be loaded into the channel 208 ofthe channel housing 204 on the centrifuge rotor assembly 568 andgenerally how this step may be affected by the operator. The word “LOAD”is also positioned above the load pictorial 744 to provide a shorttextual instruction to the operator of the required action(s). The loadpictorial 744 is also positioned to the right of the insert pictorial740 to indicate to the operator that it is preferred, although notrequired, to perform the step(s) associated with the load pictorial 744after the step(s) associated with the insert pictorial 740 have beencompleted. In order to provide further indications of the desired orderto the operator, the number “3” is also disposed adjacent to the word“LOAD.”

Finally, the loading procedure screen 732 displays a close pictorial748. The close pictorial 748 pictorially conveys to the operator thatthe door of the blood component collection device housing the centrifugerotor assembly 568 needs to be closed and generally how this step may beaffected by the operator. The word “CLOSE” is also positioned above theclose pictorial 748 to provide a short textual instruction to theoperator of the required action(s). The close pictorial 748 is alsopositioned to the right of the load pictorial 744 to indicate to theoperator that it is required to perform the step(s) associated with theclose pictorial 748 after the step(s) associated with the load pictorial744 have been completed. In order to provide further indications of thedesired order to the operator, the number “4” is also disposed adjacentto the word “CLOSE.”

In summary, the work area 688 of the loading procedure screen 732 notonly conveys to the operator what type of steps must be performed forthis aspect of the apheresis procedure and generally how to performthese steps, the work area 688 of the loading procedure screen 732 alsospecifies the order in which these steps should be performed by two“methods.” Initially, the pictorial graphics 736, 740, 744 and 748 aresequentially displayed in left-to-right fashion to specify thedesired/required order of performance. Moreover, the four steps are alsonumerically identified next to their associated one-word textualdescription.

In the event that the operator requires additional guidance with regardto any of the steps presented on the loading procedure screen 732, theoperator may touch the help button 692 provided on the loading procedurescreen 732. This may display a menu of screens which the operator mayview and/or may sequentially present a number of help screens associatedwith the loading procedure screen 732. FIG. 28 illustrates a help screen764 which relates to the loading of the blood processing vessel 352 intothe channel 208 on the channel housing 204. Note that in the case of thehelp screen 764 the upper portion of the work area 688 of the loadingprocedure screen 732 is retained (i.e., the one word textualdescriptions of the four basic steps and the associated numericalordering identifier). Moreover, the help screen 764 provides theoperator with more detail, in the nature of additional pictorials,regarding one or more aspects of the particular step(s) or substep or inthis case on the loading of the blood processing vessel 352 in thechannel 208. Once the operator exits the help screen 764 via touchingthe continue button 752 on the help screen 764, the operator is returnedto the loading procedure screen 732 of FIG. 27. Various other screens inthe graphics interface 660 may include a help button 692 to provide thistype of feature.

When the operator has completed each of the four steps or substepspresented on the loading procedure screen 732, the operator touches thecontinue button 752 on the bottom of the loading procedure screen 732.In the event that during the time in which the operator is performingthe steps or substeps associated with the loading procedure screen 732the operator wants to return to the begin operations screen 696, theoperator may touch the display screen 664 in the area of the returnbutton 756. The return button 756 may be provided on various of thescreens to return the operator to the previous screen when acceptable.Moreover, in the event that during the time in which the operator isperforming the steps or substeps associated with the loading procedurescreen 732 the operator wants to terminate the loading procedure, theoperator may touch the display screen 664 in the area of the exit loador cancel button 760. The exit load or cancel button 760 may be providedon various of the other screens to provide the operator with the optionto exit the loading procedure where appropriate.

When the operator touches the continue button 752 on the loadingprocedure screen 732, a disposable pressure test screen 768 is producedon the display 664, one embodiment of which is illustrated in FIG. 29.Generally, the disposable pressure test screen 768 pictorially conveysto the operator that certain steps must be undertaken to allow forpressure testing of the disposable set 8 and how this may be affected bythe operator. In this regard, a donor/patient access line clamppictorial 769 pictorially conveys to the operator that the bloodremoval/return tubing assembly 20, specifically the interconnect tubing38, to the donor/patient 4 must be sealed off. A donor/patient sampleline clamp pictorial 770 pictorially conveys to the operator that thesample line of the sample subassembly 46 must also be sealed off aswell. When the operator has completed these steps, the operator touchesthe continue button 752 and a test in progress screen 772 is displayedto the operator to pictorially and textually convey to the operator thatthe testing procedure is underway and such is illustrated in FIG. 30.

After the pressure test of the disposable set 8 is complete, an ACinterconnect screen 776 is produced on the display 664 and oneembodiment of which is illustrated in FIG. 31. The AC interconnectscreen 776 pictorially conveys to the operator that the anticoagulanttubing assembly 50, specifically the spike drip member 52, of theextracorporeal tubing circuit 10 needs to be fluidly interconnected withthe AC bag (not shown), as well as generally how this step may beaffected by the operator. When this step has been completed by theoperator, the operator touches the continue button 752 on the display664.

The AC interconnect is the last of the steps associated with the loadicon 704 such that the operator is returned to the master screen 696.The master screen 696 now reflects the current status of the apheresisprocedure and is illustrated in FIG. 32. That is, the color or shade ofthe load icon 704 is changed from the second color/shade to the thirdcolor/shade to that which indicates that all steps associated with theload icon 704 have been completed by the operator. Moreover, a statuscheck 730 appears on the load system button 728 in the work area 688 aswell. The load system button 728 is grayed out for the duration of theprocedure and thus indicates that the system setup may not be repeated.Consequently, two different types of indications are provided to theoperator of the current status regarding the loading procedure. Thechange in status of the donor/patient data entry portion of theapheresis procedure is also updated by presenting the information icon708 in the status bar 676 in the second color/shade which indicates tothe operator that it is now appropriate to begin this aspect of theapheresis procedure.

Whether after loading the disposable assembly as just described, orprior thereto, as mentioned above as preferred herein, the operator maythen enter donor information to assist in determining which productswill be the subject of this donation. The operator enters theinformation entry portion of the apheresis procedure by touching theinfo button 780 on the display 664 of the master screen 696. Thisproduces a donor/patient data screen 788 on the display 664, oneembodiment of which is illustrated in FIG. 33. The donor/patient datascreen 788 which includes a sex-type button 792, a height button 796,and a weight button 808. The operator may indicate the sex of thedonor/patient 4 by touching the relevant portion of the split sex-typebutton 792 and the selected sex may be displayed to the operator (e.g.,via color differentiation). Moreover, the operator may enter the heightand weight of the donor/patient 4 by touching the height button 796 andthe weight button 808, respectively. When the height button 796 andweight button 808 are engaged by the operator, a keypad 804 issuperimposed over the button whose information is to be entered asillustrated in FIG. 34. The keypad 804 may be used to enter the heightand weight of the donor/patient 4 and this information may also bedisplayed to the operator.

The information entered by the operator on the donor/patient data screen788 is used to calculate, for instance, the total blood volume of thedonor/patient 4 which is presented in a total blood volume display 790on the donor/patient data screen 788. The total blood volume of thedonor/patient 4 may be utilized in the determination of variousparameters associated with the apheresis procedure and/or in theestimation of the number and types of blood components which areanticipated to be collected in the procedure. When the operator hascompleted these data entry procedures, the operator touches the continuebutton 752 which will be displayed on the bottom of the donor/patientdata screen 788 after all requested information has been input.

A lab data entry screen 810 may also be generated on the computerdisplay 664 after the steps associated with the donor/patient datascreen 788 have been completed and as indicated by the operator, oneembodiment of which is illustrated in FIG. 35. The lab data entry screen810 requests the operator to enter the time for the collection procedureby touching a donation time button 840 which results in the keypad 804being superimposed over the donation time button 832 (not shown). Thedonation time entered by the operator will be displayed on a timedisplay 860, which specifies the duration for the procedure. Moreover,the donation time entered by the operator may also be displayed on thedonation time button 840. The donation time is used, for instance, inthe prediction of the number of the blood component(s) (e.g., red bloodcells, platelets, and/or plasma) which are anticipated to be collectedduring the procedure.

The lab data screen 810 also prompts the operator to enter thehematocrit of the donor/patient 4 by touching a hematocrit button 842.This results in the keypad 804 being superimposed over the hematocritbutton 842. The operator may then enter the hematocrit of thedonor/patient 4 (e.g., as determined via laboratory analysis of a bloodsample from the donor/patient 4) and such may be displayed on thehematocrit button 842. The hematocrit of the donor/patient 4 is alsoutilized by one or more aspects of the apheresis procedure.

The lab data screen 810 also prompts the operator to enter the plateletprecount of the donor/patient 4 by touching a platelet precount button843. This results in the keypad 804 being superimposed over the plateletprecount button 843. The operator may then enter the platelet precountof the donor/patient 4 (e.g., as determined via laboratory analysis of ablood sample from the donor/patient 4) and such may be displayed on theplatelet precount button 843. The platelet precount of the donor/patient4 is also utilized by one or more aspects of the apheresis procedure.

Once the operator has entered all of the requested information, theoperator touches the continue button 752 which then displays a procedurelisting (not shown) depicting which donation procedures this donor isqualified to undergo, and hence which blood component product orproducts this donor may donate. Preferably, such a listing will presentpreferred donation options (configurable by the blood center), such asblood center preferences and/or prioritizations for particular products(e.g., platelet products first, RBCs second; or vice versa), includingwhether double products may be favored. Then, if a particular donor isqualified to give certain products (as determined by the machine 6 basedupon the donor information entered as just described), then this listingwill so indicate with the preferences also presented. Moreover, otherprocedures may also be listed with information such as whether suchprocedures may not be qualified for this particular donor no matter thecircumstances, or perhaps certain other procedures may be listed withindications that certain further products might be qualified if certainvariable information were changeable (e.g., if more time were allowedfor a procedure). Thus, such procedures may then indicate to theoperator to return to screen 810 and change the variable information(e.g., allot more time) to then qualify that particular procedure. Alsoalternatively, certain procedures may be indicated as available if acertain amount of replacement fluid would be used with a tubing setaccording to the embodiment of FIGS. 2C-2D, for example. Thus, aselection of which tubing set to be used will also be alternativelyavailable at this point in the overall procedure. Then, when all suchselections (procedure (including priority and/or variable changes, ifany) and tubing set, e.g.) are made, the operator can then continue tothe next step; preferably loading the chosen tubing set on the machine 6in the fashion described above (see description relative to FIGS.26-41).

Then, a further continue button touch (not shown) may then return theoperator to the master screen 696 which now reflects the current statusof the apheresis procedure and as illustrated in FIG. Since all of thesteps associated with the information icon 708 have now been completed,the color/shade of the information icon 708 is changed from the secondcolor/shade to the third color/shade to convey to the operator that allassociated steps have been completed. Moreover, a status check 784appears on the donor/patient info button 780 in the work area 688 aswell. Consequently, two different types of indications are provided tothe operator of the current status of this aspect of the apheresisprocedure. Moreover, the change in status of the collection icon set 712of the apheresis procedure is updated by changing the color/shade of thedonor/patient prep icon 716 in the status bar 676 from the firstcolor/shade to the second color/shade. A run button 802 is also nowpresented on the master screen 696 such that the steps associated withthe collection icon set 712 may now be undertaken and further such thatpictorial representations of the same may be provided to the operator.

The initial screen for steps associated with the collection icon set 712is a donor/patient prep screen 812A which is illustrated in FIG. 37. Thedonor/patient prep screen 812A pictorially conveys to the operator thesteps which must be undertaken in relation to the donor/patient 4 beingfluidly interconnected with the blood component separation device.Initially, a donor/patient connect pictorial 816 is displayed whichpictorially conveys to the operator that an access needle 32 must beinstalled on the donor/patient 4, as well as generally how this step maybe affected by the operator. The word “CONNECT” is also positioned abovethe donor/patient connect pictorial 816 to provide a short textualinstruction to the operator of the required action(s). The donor/patientconnect pictorial 816 is disposed on the left side of the donor/patientprep screen 812A which indicates that this is the first step or substepassociated with the donor/patient prep icon 716. In order to providefurther indications of the desired order to the operator, the number “1”is also disposed adjacent the word “CONNECT.”

The donor/patient prep screen 812A also displays an open pictorial 820on the display 664. The open pictorial 820 pictorially conveys to theoperator that the clamps 42 in the interconnect tubing 38 and the clampin the tubing of the sample subassembly 46 must be removed, as well asgenerally how these steps may be affected by the operator. The word“OPEN” is also positioned above the open flow pictorial 820 to provide ashort textual instruction to the operator of the required action(s). Theopen pictorial 820 is disposed to the right of the donor/patient connectpictorial 816 which indicates that the step(s) associated with the openpictorial 820 should be performed only after the step(s) associated withthe donor/patient connect pictorial 816 have been completed. In order toprovide further indications of the desired order to the operator, thenumber “2” is also disposed adjacent the word “OPEN.”

The donor/patient prep screen 812A also displays a flow pictorial 824 onthe display 664. The flow pictorial 824 pictorially conveys to theoperator that there should now be a flow of blood from the donor/patient4 into the blood removal/return tubing assembly 20, specifically theblood removal tubing 22, and in the sample tubing of the samplesubassembly 46. The word “FLOW” is also positioned above the flowpictorial 824 to provide a short textual description to the operator ofwhat should be occurring at this time. The flow pictorial 824 isdisposed to the right of the open pictorial which indicates that theconditions associated with the flow pictorial 824 should occur onlyafter the step(s) associated with the open pictorial 820 have beencompleted. In order to provide further indications of the desired orderto the operator, the number “3” is also disposed adjacent the word“FLOW.”

In summary, the work area 688 of the donor/patient prep screen 812A notonly conveys to the operator what type of steps must be performed forthis aspect of the apheresis procedure and how to generally performthese steps, but also specifies the order in which these steps should beperformed by two methods. Initially, the pictorial graphics 816, 820,and 824 are sequentially displayed in left-to-right fashion. Moreover,the three steps are also numerically identified next to their associatedone-word textual description.

Once the operator completes all of the steps associated with thedonor/patient prep screen 812A, the operator touches the continue button752 which results in the display of a second donor/patient prep screen812B as illustrated in FIG. 38. The donor/patient prep screen 812Bincludes a close pictorial 828 which pictorially conveys to the operatorto terminate the flow of blood from the donor/patient 4 to the samplebag of the sample subassembly 46 by clamping the sample line andgenerally how this step may be affected by the operator. The word“CLOSE” is also positioned above the close pictorial 828 to provide ashort textual instruction to the operator of the required action(s). Theclose pictorial 828 is disposed on the left side of the donor/patientprep screen 812B which indicates that this is the first step or substepassociated with the donor/patient prep screen In order to provide anindication that this is in fact, however, the fourth step associatedwith the donor/patient preps, the number “4” is also disposed adjacentthe word “CLOSE.”

The donor/patient prep screen 812B also displays a seal pictorial 832 onthe display 664. The seal flow pictorial 832 pictorially conveys to theoperator that the sample line of the sample subassembly 46 should now besealed off and generally how this step may be affected by the operator.The word “SEAL” is also positioned above the seal pictorial 832 toprovide a short textual instruction to the operator of the requiredaction(s). The seal pictorial 832 is disposed to the right of the closepictorial 828 which indicates that the step(s) associated with the sealpictorial 832 should be performed only after the step(s) associated withthe close pictorial 828 have been completed. In order to provide furtherindications of the desired order to the operator, the number “5” is alsodisposed adjacent the word “SEAL” to indicate that this is actually thefifth step associated with the donor/patient preps.

In summary, the work area 688 of the donor/patient prep screen 812B notonly conveys to the operator what type of steps must be performed forthis aspect of the apheresis procedure and how to generally performthese steps, the work area 688 of the donor/patient prep screen 812Balso specifies the order in which these steps should be performed by twomethods. Initially, the pictorials 828, 832, and 836 are sequentiallydisplayed in left-to-right fashion. Moreover, the four steps are alsonumerically identified next to their associated one-word textualdescription.

Once the operator completes all of the donor/patient preps, the operatormay touch the start prime button 846 on the donor/patient prep screen812B which initiates the above-described blood prime of theextracorporeal tubing circuit 10 and blood processing vessel 352 andwhich results in the display of the run screen 844 illustrated in FIG.39. The run screen 844 primarily displays information to the operatorregarding the apheresis procedure. For instance, the run screen 844includes a blood pressure display 848 (i.e., to convey to the operatorthe donor/patient's extracorporeal blood pressure), a platelet collectdisplay 852 (i.e., to convey to the operator an estimate of the numberof platelets which have been currently collected), a plasma collectdisplay 856 (i.e., to convey to the operator the amount of plasma whichhas been currently collected), and a time display 860 (e.g., both theamount of time which has lapsed since the start of the collectionprocedure (the left bar graph and noted time), as well as the amount oftime remaining in the collection procedure (the right bar graph andnoted time). A control button (not shown) may be provided to togglebetween the time remaining display and the start and stop time display.

The run screen 844 may also display, in the case of a single needleprocedure (i.e., where only one needle is utilized to fluidlyinterconnect the donor/patient 4 with the blood component separationdevice 6), whether blood is being withdrawn from the donor/patient 4(e.g., by displaying “draw in progress”) or is being returned to thedonor/patient 4 (e.g., by displaying “return in progress”). Thisinformation may be useful to the donor/patient 4 in that if thedonor/patient 4 is attempting to maintain a certain blood pressure bysqueezing an article to assist in removal of blood from thedonor/patient 4, the donor/patient 4 will be provided with an indicationto suspend these actions while blood is being returned to thedonor/patient 4.

During the apheresis procedure, certain conditions may be detected bythe apheresis system 2 which would benefit from an investigation by theoperator. If one of these types of conditions is detected, anappropriate alarm screen is displayed to the operator. One embodiment ofan alarm screen 864 is illustrated in FIG. 40. Initially, the alarmscreen 864 textually conveys a potential problem with the system 2 via aproblem graphic 868. The text may be useful in ensuring that theoperator understands the problem. The alarm screen 864 also includes anaction pictorial 872 which graphically conveys to the operator theaction which should be taken in relation to the problem. These areactions which may be difficult or impossible for the system 2 to takeitself. Finally, the alarm screen includes an inspection results array876 which allows the operator to indicate the results of the inspection.In the illustrated embodiment, the array 876 includes a blood leakbutton 906, a moisture button 908, and a no leak button 910.

Depending upon the selection made by the operator on the inspectionresults array additional questions may be posed to the operator infurther screens which require further investigation and/or which specifythe desired remedial action. For instance, the supplemental alarm screen878 of FIG. 41 may be generated by the operator touching the moisturebutton 908 on the alarm screen 864. The supplemental alarm screen 878includes a remedial action pictorial 912 and remedial action text 914 toconvey to the operator how to correct the identified problem.

The computer interface 660 may also allow the operator to initiate sometype of corrective action based upon observations made by and/orconveyed to the operator. For instance, various screens of the interface660 may include a trouble shooting button 898 which will generate one ormore trouble shooting screens. These trouble shooting screens mayinclude menus or the like to allow the operator to indicate what type ofpotential problem exists.

One embodiment of a trouble shooting screen 880 is presented in FIG. 42.The trouble shooting screen 880 includes a donor/patient tingling button922. This button 922 would be utilized by the operator to attempt toremedy the effects of AC on the donor/patient 4 in response to thedonor/patient indicating a “tingling sensation” or, alternatively “ACreaction.” When the operator hits the “down arrow” of the donor/patienttingling button 922, the system 2 attempts to correct the condition in apredetermined manner (i.e., a predetermined protocol is employedpreferably this protocol does not require operator actions ordecisions). Once the tingling sensation no longer exists, the operatormay use the “up arrow” button to return the bar on the donor/patienttingling button 922 to its original position.

The trouble shooting screen 880 also includes a clumping button 924.This button 924 would be utilized by the operator if any undesiredclumping of the collected product (e.g., platelets) was observed. Whenthe operator hits the “down arrow” of the clumping button 924, thesystem 2 attempts to correct the condition in a predetermined manner(i.e., a predetermined protocol is employed and preferably this protocoldoes not require operator actions or decisions). Once the clumping is nolonger observed by the operator, the operator may use the “up arrow”button to return the bar on the clumping button 924 to its originalposition.

The trouble shooting screen 880 may also include a spillover button 916and an “air in plasma line” button 918. The spillover button 916 wouldbe engaged by the operator if red blood cells were observed in theplatelet outlet tubing 66, in the platelet collect bag 84, and/orflowing beyond the RBC dam 232. Activation of the spillover button 916via the touch screen capabilities would result in the system 2 using apredetermined and preferably automatic protocol is performed by thesystem 2 to correct this condition. Similarly, if the operator observesair in the plasma line 918 and engages the button 918, the system 2again will preferably automatically employ a predetermined protocol tocorrect this condition.

The “other problem button” 920 may be utilized to generate furthertrouble shooting screens to list further problems which may occur in theapheresis procedure. Again, preferably upon the operator touching theassociated button indicative of a particular problem, a predeterminedprotocol will be preferably automatically employed to attempt to correctthe same.

Upon completion of the collection portion of the apheresis procedure,the rinseback screen 884 is produced on the display 664 which indicatesthat the rinseback procedure will now be performed and which isillustrated in FIG. 44. Once the rinseback is completed, the color/shadeof the donate icon 720 changes from the second color to the thirdcolor/shade to indicate that all steps associated with this aspect ofthe apheresis procedure have been completed. Moreover, the color/shadeof the unload icon 724 will also change from the first color/shade tothe second color/shade to indicate to the operator that the step(s)associated therewith may now be performed.

Upon completion of the rinseback, a run finish screen may be produced onthe display 664 to provide the final collection data as illustrated inFIG. 43 (e.g., the associated yields of platelets and plasma collectedduring the procedure) as well as the fact that the procedure is over(e.g., by displaying “run completed”). The operator may then touch thecontinue button 752.

Once the rinseback procedure is completed, an unload screen 892 will bepresented on the display 664 and is illustrated in FIG. 45. The unloadscreen 892 may sequentially display a number of pictorials to theoperator to convey the steps which should be completed to terminate theprocedure. For instance, a seal/detach pictorial 900 may be initiallydisplayed on the unload screen 892 to pictorially convey to the operatorthat the tubes leading to the platelet, plasma and/or RBC collect bag(s)84, 94 and 954 should each be sealed such that the platelet, plasmaand/or RBC collect bag(s) 84, 94 and 954 respectively, may be removed.Once the operator touches the continue button 752, a disconnectpictorial 902 may be presented on the unload screen 892 to pictoriallyconvey to the operator that the access needle 32 should be removed fromthe donor/patient 4. Once the operator touches the continue button 752,a remove pictorial 904 is presented on the unload screen 892 topictorially convey to the operator that the disposable set 8 should beremoved from the blood component separation device 6 and disposed ofproperly.

The computer interface 660 provides a number of advantages. Forinstance, the computer interface 660 utilizes a three-way color/shadedifferentiation to conveniently convey the status of the apheresisprocedure to the operator. An icon is presented in one color/shade ifthe step(s) associated with the icon are not yet ready to be performed,while the icon is presented in another color/shade if the step(s)associated with the icon are ready to be performed or are beingperformed, while the icon is presented in yet another color/shade if thestep(s) associated with the icon have been completed. Moreover, thecomputer interface 660 provides pictorials to the operator of at leastcertain of the steps of the apheresis procedure. Furthermore, thedesired/required ordering of at least the fundamental steps of theapheresis procedure is conveyed to the operator. Finally, the interface660 allows for correction of certain conditions, which after appropriateoperator input, are remedied by the system 2 in accordance with apredetermined protocol.

The foregoing description of the present invention has been presentedfor purposes of illustration and description. Furthermore, thedescription is not intended to limit the invention to the form disclosedherein. Consequently, variations and modifications commensurate with theabove teachings, and skill and knowledge of the relevant art, are withinthe scope of the present invention. The embodiments describedhereinabove are further intended to explain best modes known ofpracticing the invention and to enable others skilled in the art toutilize the invention in such, or other embodiments and with variousmodifications required by the particular application(s) or use(s) of thepresent invention. It is intended that the appended claims be construedto include alternative embodiments to the extent permitted by the priorart.

1. A method for extracorporeal collection of blood components from adonor/patient comprising: removing blood from a donor/patient through asingle needle; flowing said blood into a dual stage blood processingvessel; separating plasma from said blood within said blood processingvessel; collecting at least a portion of said plasma in a plasmacollection reservoir separate from said blood processing vessel;separating red blood cells from said blood within said dual stage bloodprocessing vessel; collecting at least a portion of Mid separated redblood cells in a red blood cell collection reservoir separate from saidblood processing vessel, wherein said plasma separation and collectionsteps are completed at least partially contemporaneously with said redblood cell separation and collection steps; returning uncollected bloodcomponents of said blood to said donor/patient through said singleneedle; and replacing fluid volume in said donor/patient by flowing areplacement fluid to said donor/patient through said single needle.
 2. Amethod as recited in claim 1, whereby the red blood cell collecting stepprovides for obtaining a double volume of collected red blood cells. 3.A method as recited in claim 2 in which said double volume of collectedred blood cells totals substantially about 400 milliliters contained intwo substantially separate reservoirs.
 4. A method as recited in claim1, wherein said plasma collection step is completed at least partiallyseparately from said red blood cell collection step.
 5. A method asrecited in claim 1, wherein prior to said red blood cell collectionstep, and separate from said plasma collection step, said method furthercomprises a red blood cell collection set-up phase including:establishing a hematocrit of at least about 80 within said separated redblood cells within said blood processing vessel and an AC ratio withinsaid blood at about
 8. 6. A method as recited in claim 5, furthercomprising maintaining said hematocrit and AC ratio during said redblood cell separation and collection steps.
 7. A method as recited inclaim 1 in which said step of delivering a replacement fluid includesflowing replacement fluid at a rate equal to the total flow rate ofcollected blood components multiplied by the desired fluid balancepercentage resulting within the donor/patient.
 8. A method as recited inclaim 7 in which said step of delivering a replacement fluid includespumping replacement fluid at a rate equal to the total flow rate ofcollected fluids minus the inlet flow rate of anticoagulant multipliedby the desired fluid balance percentage resulting within thedonor/patient.
 9. A method as recited in claim 7 in which a replacementfluid is pumped from a source first to an intermediate reservoir priorto ultimate delivery to the donor/patient.
 10. A method as recited inclaim 7 in which a replacement fluid is delivered to the donor/patientin a bolus.
 11. A method as recited in claim 7 in which a replacementfluid is delivered to the donor/patient in a substantially continuousfashion.
 12. A method as recited in claim 1 further comprising:retaining the separated red blood cells in a first stage of theprocessing vessel; establishing a pre-determined packing factor for theseparated red blood cells within said blood processing vessel; andflowing the red blood cells to red blood cell outlet.
 13. A method asrecited in claim 12 in which said collecting step further includes astep for collecting at least a portion of the separated plasma in aplasma collection reservoir separate from said blood processing vesselto establish collected plasma; and wherein said plasma collection stepis performed at least partially contemporaneously with said red bloodcell collection step.
 14. A method as recited in claim 13, wherein saidplasma collection step is performed prior to said red blood cellcollection step.
 15. A method as recited in claim 13, wherein saidplasma collection step is performed at least partially alter said redblood cell collection step.
 16. A method as recited in claim 13, whereinsaid red blood cell collection step is performed at least partiallyafter said plasma collection step.
 17. A method as recited in claim 11further comprising establishing a packing factor of at least about 13for the separated red blood cells within said blood processing vessel.18. A method as recited in claim 17 wherein said packing factor isbetween 11 and
 21. 19. A method as recited in claim 18 wherein saidpacking factor is at least about
 13. 20. A method as recited in claim 19in which the packing factor is about
 16. 21. A method as recited inclaim 17 which further includes establishing an AC ratio in tho bloodprocessing vessel of between about 6 and about
 16. 22. A method asrecited in claim 17 in which the packing factor is about 16 during thecontemporaneous collection of separated plasma and separated red bloodcell and the packing factor is then reduced to about 13 during the atleast partial step of collecting separated red blood cells after theperformance of the collection of separated plasma.
 23. A method asrecited in claim 1, further comprising a set up step prior to saidcollecting steps; said set up step comprising: flowing the separatedblood components Out of said blood processing vessel, whereinsubstantially all of said separated blood components flowing out of theblood processing vessel are accumulated for re-infusion to adonor/patient during the set-up step.
 24. A method as recited in claim23, wherein said blood is flowed into said blood processing vessel at aninlet flow rate, and said set-up step comprises: reducing said inletflow rate.
 25. A method as recited in claim 23, wherein said bloodprocessing vessel is rotated at an rpm rate, and wherein said set-upstep comprises: increasing said rpm rate.
 26. A method as recited inclaim 1, wherein said processing vessel includes a first stage and asecond stage, the second stage being separated from said first stage bya dam, a blood inlet for communicating blood into the first stage, aplasma outlet disposed in the second stage and a red blood cell outletdisposed in the first stage; and wherein during said plasma collectionstep, said method further comprises: separating plasma from said bloodwithin said centrifugal dual stage blood processing vessel to establishseparated plasma, whereby a portion of the separated plasma flows overthe dam in the processing vessel to the plasma outlet in the secondstage of the processing vessel; separating red blood cells from saidblood within said centrifugal dual stage blood processing vessel toestablish separated red blood cells whereby the separated red bloodcells remain in the first stage of the processing vessel and flow to thered blood cell outlet; and recirculating a portion of the uncollectedseparated blood components into said blood processing vessel.
 27. Adevice for extracorporeal separation and collection of blood componentsfront a donor/patient, comprising: a centrifugal blood processingchannel into which blood from a donor/patient is adapted to be flowed,and in which said blood is separated into at least separated plasma andseparated red blood cells; said centrifugal dual stage blood processingchannel including a first stage and a second stage, the second starebeing separated from said first stage by a dam, a blood inlet forcommunicating blood into the first stage, a plasma outlet disposed inthe second stage and a red blood cell outlet disposed in the firststage; said centrifugal blood processing channel being adapted to beused with: a removable plasma collection reservoir operably connected tosaid centrifugal blood processing channel, whereby into which at least aportion of said separated plasma is collected; a removable red bloodcell collection reservoir operably connected to said blood processingchannel whereby a portion of said separated red blood cells arecollected in said red blood cell collection reservoir, and a replacementfluid assembly which is operably connectable to the donor/patient;wherein said replacement fluid assembly is adapted to deliverreplacement fluid to the donor/patient.
 28. A disposable blood tubingset adapted to be used with a device for extracorporeal separation andcollection of blood components from a donor/patient, said disposableblood tubing set comprising: a disposable centrifugal dual stage bloodprocessing vessel into which blood from a donor/patient is adapted to beflowed, and in which said blood is separated into at least separatedplasma and separated red blood cells; said centrifugal dual stage bloodprocessing vessel including a firs: stage and a second stage, the secondstage being separated from said first stage by a dam, a blood inlet forcommunicating blood into the first stage, a plasma outlet disposed inthe second stage and a red blood cell outlet disposed in the firststage; a plasma collection reservoir operably connected to saidcentrifugal blood processing vessel, whereby into which said plasmacollection reservoir at least a portion of said separated plasma iscollected; a red blood cell collection reservoir operably connected tosaid blood processing vessel whereby a portion of said separated redblood cells are collected in said red blood cell collection reservoir;and a disposable fluid flow cassette assembly operably interconnected tosaid centrifugal blood processing vessel, said cassette assembly havingan intermediate reservoir disposed therein, said intermediate reservoirbeing adapted to receive separated uncollected blood components fromsaid centrifugal blood processing vessel; and a replacement fluidassembly which is operably connected to said fluid flow cassette andsaid intermediate reservoir; wherein said replacement fluid assembly isadapted to deliver replacement fluid to said intermediate reservoir forsubsequent infusion of the replacement fluid into a donor/patient.